Term
| GI Tract - Organization of Layers - Inner to Outer |
|
Definition
Epithelium - surface lining
Lamina Propria - loose vascular tissue, contains epithelial glands
Muscularis Mucosae - smooth muscle layer, controls microperistalsis_x000D_ Submucosa - soft tissue surrounding mucosa_x000D_ Muscularis Propria - inner circular, outer longitudinal - smooth muscle controls peristalsis_x000D_ Serosa (Peritoneum) or Adventitia |
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Term
| GI Tract - Epithelial Overview |
|
Definition
Esophagus - squamous, no mucin or villi, neutral pH, endogenous bacteria_x000D_
Stomach - gastric, neutral mucin, no villi, acidic pH, no bacteria_x000D_
Small Intestine - columnar, acidic mucin, micro villi, neutral pH, endogenous bacteria_x000D_
Colon - columnar, acidic mucin, no villi, neutral pH, endogenous bacteria |
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Term
| GI Tract - Ganglion Cells |
|
Definition
Meissner's Submucosal Plexus - runs through submucosa, innervates glands_x000D_
Auerbach's Myenteric Plexus - runs between muscularis propria layers, innervates smooth muscle_x000D_
Both carry parasympathetic fibers |
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Term
| GI Tract - Stem Cell Niche |
|
Definition
Stem cells located at base of crypt_x000D_
Wnt signaling from supporting stroma promotes epithelial proliferation_x000D_
Mutations in Wnt signaling pathway lead to dysplasia and carcinoma |
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Term
| GI Tract - Adult Structures Derived From Embryonic Foregut |
|
Definition
Pharynx and Esophagus_x000D_
Stomach_x000D_
1st and 2nd parts of Duodenum - up to entry point of common bile duct_x000D_
Innervated by Parasympathetic Vagus and Sympathetic T5-T9_x000D_
Arterial blood supply to structures below diaphragm from Celiac Trunk |
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Term
| GI Tract - Adult Structures Derived From Embryonic Midgut |
|
Definition
2nd, 3rd, and 4th parts of Duodenum - from entry point of common bile duct_x000D_
Jejunum, Ileum, Cecum and Appendix_x000D_
Ascending and Proximal 2/3 of Transverse Colon_x000D_
Innervated by Parasympathetic Vagus and Sympathetic T10-T12_x000D_
Arterial blood supply from Superior Mesenteric Artery |
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|
Term
| GI Tract - Adult Structures Derived From Embryonic Hindgut |
|
Definition
Distal 1/3 of Transverse Colon_x000D_
Descending, Sigmoid Colon, Rectum and Upper Anal Canal_x000D_
Innervated by Parasympathetic S2,3,4 and Sympathetic L1-L3_x000D_
Arterial blood supply from Inferior Mesenteric Artery |
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|
Term
| GI Tract - Boundaries Between Fore/Mid/Hindgut Structures |
|
Definition
Foregut / Midgut = entry point of common bile duct in Duodenum_x000D_
Midgut / Hindgut = 2/3 of the distance of the transverse colon |
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Term
| GI Tract - Autonomic Innervation |
|
Definition
Foregut - Parasympathetic Vagus and Sympathetic Thoracic Splanchnics T5-T9_x000D_
Midgut - Parasympathetic Vagus and Sympathetic Thoracic Splanchnics T10-T12_x000D_
Hindgut - Parasympathetic Pelvic Splanchnics S2-S4 and Sympathetic Lumbar Splanchnics L1-L3_x000D_
Sympathetics pain fibers - referred to dermatomes of body wall matching segmental innervation |
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Term
| GI Tract - Peritoneum Layers |
|
Definition
Parietal Peritoneum - closest to body wall_x000D_
Visceral Peritoneum - attached to surface of GI tract organs_x000D_
Mesentary - double layer of parietal and visceral peritoneum_x000D_
Peritoneal Cavity - potential space formed between parietal and visceral peritoneum |
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|
Term
| GI Tract - Distribution of Dorsal and Ventral Mesentary |
|
Definition
Entire GI tract below diaphragm has dorsal mesentary_x000D_
Only foregut also has ventral mesentary |
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Term
| GI Tract - Embryonic Foregut Structure Movement |
|
Definition
Foregut rotates 90 degrees to right about long axis_x000D_
Liver moves from ventral midline to left, suspended in ventral mesentary_x000D_
Stomach rotates to right, suspended in dorsal and ventral mesentary_x000D_
Spleen moves from dorsal midline to right, suspended in dorsal mesentary_x000D_
Pancreas (except tail) adheres to posterior body wall - becomes secondarily retroperitoneal |
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|
Term
| GI Tract - Adult Structure Remnants of Embryonic Mesenteries |
|
Definition
Falciform ligament - connects liver to anterior body wall - ventral mesentary_x000D_
Lesser Omentum - connects liver to lesser curvature of stomach - ventral mesentary_x000D_
Greater Omentum - connects greater curvature of stomach to spleen and GI tract - dorsal mesentary_x000D_
Epiploic foramen - opening to omental bursa - lesser sac of lesser omentum |
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|
Term
| GI Tract - Embryonic Midgut Structure Movement |
|
Definition
Midgut rotates 270 degrees counterclockwise about axis of superior mesenteric artery_x000D_
Forms three sided "picture frame" with colon - cecum in lower right |
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|
Term
| GI Tract - Entry of IVC, Esophagus, and Aorta into Abdomen |
|
Definition
I Ate Ten Eggs At 12_x000D_
IVC - T8_x000D_
Esophagus - T10_x000D_
Aorta - T12 |
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Term
| GI Tract - Ligament of Treitz |
|
Definition
Suspensory ligament of duodenum - connects duodenum to diaphragm_x000D_
Band of skeletal muscle arising from diaphragm and fibromuscular smooth muscle from duodenum_x000D_
Inserts at duodenojejunal flexure - contraction widens angle, allows passage of contents_x000D_
Hematemesis (blood in vomit) or melena (black tarry stool) indicate bleed proxmial to ligament_x000D_
Hematochezia (red blood or clots in stool) indicate bleed distal to ligament |
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|
Term
| GI Tract - Esophagus Muscle Composition |
|
Definition
Proximal 5% - voluntary skeletal muscle_x000D_
Middle 45% - mostly smooth muscle, some skeletal_x000D_
Distal 50% - involuntary smooth muscle_x000D_
Smooth Muscle - inner circular, outer longitudinal layers |
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|
Term
| GI Tract - Anatomic Divisions of Stomach |
|
Definition
Cardiac - entry point of esophagus, epithelial transition point_x000D_
Fundus - superior lobe extending above cardiac notch_x000D_
Body - large central area bounded by cardia, fundus, and pylorus_x000D_
Pylorus - antrum and canal, connects body to duodenum |
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|
Term
| GI Tract - Stomach Muscle Composition |
|
Definition
Outer longitudinal_x000D_
Middle circular_x000D_
Inner oblique |
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Term
| GI Tract - Gastroesophageal Junction |
|
Definition
Located 1.25 cm below diaphragm in abdomen_x000D_
Squamo-columnar cell juntion - forms Z line - cardia_x000D_
Esophageal squamous epithelium meets gastric oxyntic mucosal epithelium_x000D_
Site of physiologic inferior esophageal sphincter |
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Term
| GI Tract - Parasympathetic Gastric Innvervation |
|
Definition
Right Vagus Nerve --> Posterior Vagal Trunk --> Posterior Gastric Branches_x000D_
Left Vagus Nerve --> Anterior Vagal Trunk --> Anterior Gastric Branches |
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Term
| GI Tract - Gastric Arterial Blood Supply |
|
Definition
Left and Right Gastric Arteries supply Lesser Curvature_x000D_
Left Gastric A. from Celiac Trunk and Right Gastric A. from Common Hepatic_x000D_
Left and Right Gastroepiploic Arteries supply Greater Curvature_x000D_
Left GE A. from Gastroduodenal A. and Right GE from Splenic A. |
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|
Term
| GI Tract - Anatomic Differences Between Jejunum and Ileum |
|
Definition
J - plica circularis mucosal folds, simple arterial arcades, long vasa recta_x000D_
I - smooth mucosal wall, Peyer's patches, complex arterial arcades, short vasa recta |
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Term
| GI Tract - Major Aortic Branches Supplying GI Structures |
|
Definition
Celicac Trunk - Splenic A, Left Gastric A, Common Hepatic A_x000D_
Superior Mesenteric Artery - Middle Colic A, Right Colic A, Ileocolic A_x000D_
Inferior Mesenteric Artery - Left Colic A, Superior Rectal A, Sigmoid A |
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Term
| GI Tract - Epithelial Cell Adhesion Structures |
|
Definition
Tight Junctions - apical domain, cadherin based, attached to microtubules_x000D_
Desmosomes - attach cell surface ahdesion proteins to keratin cytoskeleton (intermediate filaments)_x000D_
Gap Junctions - directly connect cytoplasm through hydrophillic channels |
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Term
| GI Tract - Esophagus Histology |
|
Definition
Non Keratinizing stratified squamous epithelium_x000D_
Thick muscularis mucosae layer_x000D_
Salivary like glands under muscularis mucosae to lubricate esophageal lumen |
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Term
| GI Tract - Gastric Chief Cell |
|
Definition
Located in oxyntic mucosa of gastric corpus_x000D_
Basophilic H&E appearance - large amount of ER_x000D_
Secretes pepsinogen, gastric lipase, and rennin |
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Term
| GI Tract - Brunner Glands |
|
Definition
Located exclusively in duodenum_x000D_
Produce mucus rich alkaline secretion containing bicarbonate_x000D_
Provides protection from gastric acid and raises pH to activate digestive enzymes |
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|
Term
| GI Tract - Sliding Hiatal and Paraesophageal Hernias |
|
Definition
Sliding Hiatal - movement of GE junction into throacic cavity_x000D_
Paraesophageal - Portion of stomach herniates through esophageal hiatus into thoracic cavity |
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Term
| GI Tract - Complications of a Posterior Duodenal Ulcer |
|
Definition
Can erode into gastroduodenal artery - massive hemorrhage_x000D_
Direct suture ligation of ulcer +/- feeding vessels_x000D_
Gastroduodenal A, anterior superior pancreaticoduodenal A. right gastroepiploic A. |
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Term
| GI Tract - Surgical Treatment of Peptic Ulcer Disease |
|
Definition
Vagotomy and Pyloroplasty_x000D_
Bitruncal vagotomy at level of distal esophagus - removes vagal stimulation of acid secretion_x000D_
Pylorus rendered incompetent, stays open, to allow gastric drainage_x000D_
Can selectively lesion anterior vagal branch_x000D_
Preserve posterior vagal nerves of latarjet, antral innervation maintained, no pyloroplasty needed |
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|
Term
| GI Tract - Surgical Treatment of Gastroesophageal Refulx Disease |
|
Definition
Fundoplication - Nissen method_x000D_
Fundus of stomach mobilized by removing short gastric vessels_x000D_
Fundus wrapped around distal esophagus_x000D_
Crura of diaphragm repositioned to repair hiatal hernia |
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Term
| GI Tract - Appendix Arterial Blood Supply |
|
Definition
| Appendicular Artery off Ileal branch of Ileocolic Artery |
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|
Term
| GI Tract - Esophageal Rings |
|
Definition
A Ring - muscular ring, transition from tubular esophagus to phrenic ampulla_x000D_
B Ring - mucosal ring, esophagogastric junction, band of mucosa and submucosa_x000D_
C Ring - diaphragmatic impression if there is a hiatal hernia |
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|
Term
| GI Tract - Gallstone Radiology |
|
Definition
Peripheral rim of calcification_x000D_
Layers of calcification around cholesterol nidus in gallbladder |
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Term
| Radiology - XR v CT - spatial resolution and contrast resolution |
|
Definition
XR has greater spatial resolution_x000D_
CT has greater contrast resolution |
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Term
| GI Tract - Barium Sulfate |
|
Definition
Inert element, coated with suspension agents_x000D_
Coats mucosal surface, fills grooves_x000D_
XR beam attenuated by barium, appears white |
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|
Term
|
Definition
Band of smooth muscle cross gastric cardia obliquely_x000D_
Help create angle of esophagus and stomach |
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|
Term
| GI Tract - Phrenoesophageal Ligament |
|
Definition
Tethers esophagus to esophageal hiatus of the diaphragm_x000D_
Loose enough to allow esophagus to elevate and shorten during swallowing_x000D_
Degenerates with age |
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Term
| GI Tract - Agents That Decrease Lower Esophageal Sphincter Pressure |
|
Definition
Anticholinergics, barbituates, calcium channel blockers, diazepam, dopamine, theophylline_x000D_
Caffeine, theobromine (chocolate), peppermint, ethanol, fat, smoking_x000D_
CCK, glucagon, estrogen, somatostatin, secretin_x000D_
Lower sphincter pressure results in more frequent reflux |
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|
Term
|
Definition
Large folds in gastric fundus and gastric body, no folds in antrum_x000D_
Composed of mucosa and submucosa_x000D_
Appear as smooth, tubular, radiolucent fillings in barium imaging |
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|
Term
| GI Tract - Gastric Foveolar and Glandular Layers |
|
Definition
Foveolae are conical depressions in mucosal surface, connect to gastric glands, lined by mucous cells_x000D_
Gastric Body - foveolae are upper 1/3, glands are lower 2/3_x000D_
Gastric Antrum - foveolae are upper 1/2, glands are lower 1/2 |
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Term
| GI Tract - Distinguishing Feature of Gastric Body Mucosa |
|
Definition
| Presence of chief and parietal cells |
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|
Term
| GI Tract - Areae Gastricae |
|
Definition
Imaging pattern on barium study of stomach_x000D_
Fine reticular network, polygonal areas_x000D_
Most abundant in antrum, some present in fundus |
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Term
| GI Tract - Valculae Conniventes |
|
Definition
Small intestine mucosal folds perpendicular to longitudinal axis_x000D_
Contain mucosa and submucosa layers_x000D_
Increase surface area for absorption by 300%_x000D_
Taller, thicker, and more abundant in jejunum than ileum_x000D_
Radiologic abnormality suggests pathology in mucosa or submucosa_x000D_
Appear large like thumbprints with submucosal edema or hemorrhage on mesenteric border |
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Term
| GI Tract - Pylorus Muscular Layer |
|
Definition
Two thick bands fused superiorly at a bulge or torus_x000D_
Pylorus contracts, mucosa may bulge outward between bands_x000D_
Barium outpouching termed torus defect |
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|
Term
| GI Tract - Colon Arterial Supply Anatomic Orientation |
|
Definition
Arteries course through mesentery_x000D_
Attach to colon at mesenteric border_x000D_
Enter colonic wall on mesenteric domain of antimesenteric teniae_x000D_
Wall weakness at site of arterial perforation, site of diverticula formation |
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|
Term
| GI Tract - Colon Longitudinal Muscle Layer |
|
Definition
Coalesce into three distinct bands - teniae coli_x000D_
Haustral sacculations result from tension of teniae coli_x000D_
Stretches from cecum to beginning of rectum_x000D_
Fuse into single layer at rectum |
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|
Term
| GI Tract - Aphthoid Ulcers |
|
Definition
Occur at sites of lymph aggregates in the colon or small intestine_x000D_
Lymph tissue becomes inflamed, overlying mucosa ulcerates_x000D_
Earliest lesion in Crohns Disease_x000D_ |
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|
Term
| GI Tract - Colon and Rectum Lymphatic Drainage |
|
Definition
Right / Ascending and Proximal Transverse Colon drain up branches of the SMA_x000D_
Left / Descending Colon drain up branches of the IMA_x000D_
Anal Canal (including 2 cm above pecinate line) drain to inguinal lymph nodes |
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Term
| GI Tract - Liver Venous Divisions |
|
Definition
Middle Hepatic Vein divides liver into left and right lobes_x000D_
Left Hepatic Vein divides left lobe into medial and lateral segment_x000D_
Right Hepatic Vein divides right lobe into anterior and posterior segments_x000D_
All Hepatic Veins converge at dome of liver to join IVC |
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Term
| GI Embryonic Development - Gut Tube Openings |
|
Definition
Cranial end (foregut) terminates at buccopharyngeal membrane - future oral cavity_x000D_
Caudal end (hindgut) terminates at cloacal membrane - future rectum_x000D_
Opening to yolk sac narrows to form vitelline duct - becomes incorporated into umbilical cord |
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|
Term
| GI Embryonic Development - Occlusion and Recanalization |
|
Definition
Week 5 - hollow gut tube_x000D_
Week 6 - endodermal epithelial proliferation results in occluded gut tube_x000D_
Weeks 7-8 - tissue degenerates by vacuole formation to recanalize (open) gut tube_x000D_
Week 9 - endodermal lining differentiates into definitive mucosal epithelium_x000D_
Failure of complete or normal recanalization results in duplication, stenosis, or atresia |
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Term
| GI Embryonic Development - Formation of Lung Rudiment |
|
Definition
Respiratory diverticulum bud forms at day 22_x000D_
Ventral out pouching of thoracic esophagus_x000D_
Sequential bifurcation of lung bud to bronchial buds resulting in terminal sacs |
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Term
| GI Tract - Esophageal Atresia and Stenosis |
|
Definition
Complete blockage or narrowing of esophagus_x000D_
Usually due to failure of recanalization_x000D_
85% associated with tracheoesophageal fistula |
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|
Term
| GI Tract - Tracheoesophageal Fistula |
|
Definition
Caudal displacement of septum between trachea and esophagus_x000D_
Results in incomplete separation of respiratory and esophageal tubes_x000D_
Fetus cannot swallow and dispose of amniotic fluid - fluid accumulates resulting in polyhydramnios_x000D_
Newborn first swallow is normal, then fluid suddenly expelled and enters respiratory distress_x000D_ |
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Term
| GI Tract - Congenital Hiatal Hernia |
|
Definition
Failure of esophagus to elongate - short esophagus_x000D_
Displaces / pulls part of stomach into thoracic cavity |
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Term
| GI Embryonic Development - Stomach Formation |
|
Definition
Dorsal wall grows more rapidly than ventral wall_x000D_
Forms greater curvature (dorsal) and lesser curvature (ventral)_x000D_
Differential thinning of right side of dorsal mesentery_x000D_
90 degree rotation of stomach around craniocaudal axis_x000D_
Greater curvature ends on left and lesser curvature ends on right_x000D_
Rotation results in displacement of duodenum - adheres to dorsal body wall |
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Term
| GI Tract - Congenital Hypertrophic Pyloric Stenosis |
|
Definition
Thickening of pylorus_x000D_
Severe stenosis and obstruction of food passage_x000D_
Newborns display distended stomach and projectile vomiting |
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|
Term
| GI Tract - Duodenal Atresia and Stenosis |
|
Definition
Complete blockage or narrowing of duodenal lumen_x000D_
Usually due to failure of recanalization_x000D_
Newborn vomiting within hours of birth - vomit contains bile_x000D_
Atresia occurs in 30% of infants with Down's Syndrome and 20% of premature births_x000D_
"Double Bubble" appearance on ultrasound - stomach and proximal duodenum dilated and filled with air_x000D_ |
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|
Term
| GI Embryonic Development - Liver Formation |
|
Definition
Hepatic Plate - endodermal thickening appears on ventral side of duodenum_x000D_
Hepatic plate proliferates to form hepatic diverticulum - grows into ventral mesentery_x000D_
Diverticulum gives rise to hepatic cords, bile canaliculi, and hepatic ducts_x000D_
Hepatic cords develop into hepatocytes_x000D_
Ventral mesentery connecting liver to stomach becomes lesser omentum_x000D_
Ventral mesentery connecting liver to ventral body wall becomes falciform ligament |
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|
Term
| GI Embryonic Development - Gallbladder and Cystic Duct Formation |
|
Definition
Cystic Diverticulum forms as second endodermal thickening on ventral side of duodenum_x000D_
Forms caudal to hepatic diverticulum_x000D_
Gallbladder and Cystic Duct form Cystic Diverticulum_x000D_
Cells at junction of hepatic and cystic ducts proliferate to form the bile duct |
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|
Term
| GI Tract - Extrahepatic Biliary Atresia |
|
Definition
Obstruction of bile duct_x000D_
Due to failure of canalization or fetal liver infection_x000D_
Jaundice develops soon after birth |
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|
Term
| GI Embryonic Development - Pancreas Formation |
|
Definition
Dorsal Pancreatic bud forms on duodenum opposite the hepatic diverticulum - grows into dorsal mesentery_x000D_
Ventral Pancreatic bud forms on ventral duodenum caudal to gallbladder - grows into ventral mesentery_x000D_
Ventral bud gives rise to hepatobiliary tree - main duct of ventral bud connects to bile duct_x000D_
Bile duct and ventral pancreatic duct migrate around duodenum to dorsal mesentery_x000D_
Pancreatic ducts fuse - dorsal pancreatic duct degenerates_x000D_
Head, neck, and body of pancreas fuse to dorsal body wall - tail remains peritoneal |
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|
Term
| GI Tract - Anular Pancreas |
|
Definition
Two ventral pancreatic buds form - rotate in opposite directions to fuse with dorsal bud_x000D_
Thin band of pancreatic tissue surrounds duodenum_x000D_
Can cause duodenal atrestia or stenosis - either at birth, or after inflammation or malignancy |
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|
Term
| GI Embryonic Development - Midgut Formation |
|
Definition
Primary intestinal loop - hairpin loop surrounding SMA - tip of turn attached to umbillicus by the vitelline duct_x000D_
Cranial loop gives rise to ileum, caudal loop gives rise to midgut colon_x000D_
Loop herniates into umbillicus and rotates 90 degrees to the right_x000D_
Loop retracts into abdominal cavity and rotates 180 degrees to the right_x000D_
Total 270 degree turn counterclockwise / right _x000D_ |
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|
Term
| GI Tract - Congenital Omphalocele |
|
Definition
Herniation of intestines into umbilical cord_x000D_
Failure of midgut to retract into abdominal cavity at week 10_x000D_
Intestinal loops protrude from abdominal wall through umbilical cord, surrounded by amniotic membrane_x000D_ |
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|
Term
| GI Tract - Umbilical Hernia |
|
Definition
Midgut retracts normally into abdominal cavity at week 10_x000D_
Failure of umbilicus to close completely_x000D_
Intestine herniates into umbilical cord |
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|
Term
|
Definition
Extrusion of midgut structures through ventral body wall_x000D_
Due to incomplete lateral folding during week 4_x000D_
Involves all layers of abdominal wall from peritoneum to skin_x000D_
No involvement of umbilical cord_x000D_ |
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|
Term
| GI Tract - Ileal (Merkel's) Diverticulum |
|
Definition
Persistent remnant of stalk connecting yolk sac to GI lumen_x000D_
True diverticulum, contains all layers of GI wall_x000D_
May contain gastric or pancreatic tissue_x000D_
Can cause appendicitis-like complications and symptoms_x000D_
Present in 2% of population within 2 feet of ileocecal valve, if symptomatic present by age 2 (rule of 2s) |
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|
Term
| GI Tract - Embryonic Rotation Defects |
|
Definition
Nonrotation - left sided colon, second 180 degree rotation does not occur_x000D_
Mixed rotation - failure to complete final 90 degree rotation, cecum ends inferior to stomach_x000D_
Reversed rotation -second 180 degree rotation reversed, duodenum and transverse colon moved_x000D_
Cecum unattached in abnormal location - risk of internal rotation, hernia, ischemic twisting_x000D_ |
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|
Term
| GI Tract - Midgut Volvulus |
|
Definition
Twisting of the intestines_x000D_
Due to failure of midgut to retract normally into abdomen and failure of normal fixation to body wall_x000D_
Can result in blockage of gut lumen and blood supply to gut tissue |
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|
Term
| GI Embryonic Development - Rectum and Urogenital Sinus Formation |
|
Definition
Cloaca formation - distal hindgut formation sealed by cloacal membrane_x000D_
Urorectal septum divides cloaca into posterior rectum and anterior urogenital sinus_x000D_
Urorectal septum formed from fusion of superior Tourneux fold and two lateral Rathke folds_x000D_
Urogenital membrane and anal membrane fuse at perineum_x000D_
Anal membrane proliferates to form anal pit - invaginates to form anal canal |
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|
Term
| GI Tract - Congenital Megacolon / Hirschprung's Disease |
|
Definition
Failure of neural crest cell migration during weeks 5-7_x000D_
Partial absence of enteric ganglion plexus_x000D_
Results in localized failure of peristalsis and dilation proximal to blockage_x000D_
Most common cause of neonatal colon obstruction |
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|
Term
| GI Tract - Membranous Atresia |
|
Definition
Anus is in normal position but sealed by anal membrane_x000D_
Failure of anal membrane perforation during week 8 |
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|
Term
| GI Histology - Presence of Villi |
|
Definition
| Exclusively small intestine |
|
|
Term
| GI Histology - Presence of submucosal glands |
|
Definition
|
|
Term
| GI Histology - Areas Surrounded by Adventitia |
|
Definition
Esophagus - above peritoneal cavity_x000D_
Rectum and Anus - below peritoneal cavity_x000D_
Mid and Lower duodenum - retroperitoneal_x000D_
Posterior Surface of Ascending and Descending Colon - retroperitoneal |
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|
Term
| GI Histology - Stomach Regions and Cell Types |
|
Definition
Cardia - mostly mucous secreting cells_x000D_
Fundus and Body - Parietal Cells, Chief Cells, and Enteroendocrine cells_x000D_
Antrum and Pylorus - G cells, enteroendocrine cells, and mucous cells |
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|
Term
| GI Histology - Gastric Glands |
|
Definition
Foveolae / pits - upper portion, contain mucous secreting cells_x000D_
Isthmic zone - connects pits and neck, contains epithelial stem cells_x000D_
Neck - Parietal cells and mucous cells_x000D_
Basal - deepest portion, contains chief cells, enteroendocrine cells, and enterochromaffin-like cells_x000D_
2-7 deep glands empty into a single pit |
|
|
Term
| GI Histology - Parietal Cells |
|
Definition
Pink eosinophilic cytoplasm - abundant mitochondria_x000D_
Secrete acid and Intrinsic factor - binds B12 for absorption_x000D_
H+/K+/ATPase contained in membrane of Tubulovesicles - rapidly inserted into surface membrane_x000D_ |
|
|
Term
| GI Histology - Chief Cells |
|
Definition
Blue basophilic cytoplasm - abundant rER_x000D_
Secretory granules contain pepsinogen and weak lipases |
|
|
Term
| GI Tract - Entry of Bile and Pancreatic Ducts into Duodenum |
|
Definition
Fusion of both ducts forms Ampulla of Vater_x000D_
Sphincter of Oddi regulates content release_x000D_
Penetrates medial wall of second part of duodenum |
|
|
Term
| GI Histology - Small Intestine Crypt Cells |
|
Definition
Paneth cells - secrete defensins, lysozyme, and TNFa_x000D_
Enteroendocrine cells - secretory granules in basal domain, secrete contents into bloodstream - CCK and secretin_x000D_
CCK stimulates gallbladder bile release, secretion of pancreatic enzymes, and slows gastric emptying_x000D_
Secretin stimulates pancreatic bicarbonate secretion and enhances insulin secretion_x000D_ |
|
|
Term
| GI Histology - Large Intestine / Colon |
|
Definition
Straight glands_x000D_
No villi_x000D_
Mucous secreting goblet cells, absorptive cells, and enteroendocrine cells_x000D_
Gut Associated Lymphoid Tissue (GALT/MALT) - not distinct Peyer's patches |
|
|
Term
| GI Histology - Location of Peyer's Patches |
|
Definition
|
|
Term
| Esophagus - Diseases Differentially Affecting Upper v Lower Esophagus |
|
Definition
Upper Striated - polymyositis, myasthenia gravis_x000D_
Lower Smooth - scleroderma, achalasia |
|
|
Term
| Esophagus - Upper Esophageal Sphincter |
|
Definition
Separates pharynx from esophagus_x000D_
Inferior pharyngeal constrictor, circopharyngeus, and cervical esophagus muscles_x000D_
Pressure decreases to allow food into esophagus, belching and vomiting_x000D_
Pressure increases to prevent air entry into GI tract and reflux of gastric contents into pharynx_x000D_
Basal tonic muscle contraction tone - transiently inhibited to reduce pressure during swallowing_x000D_ |
|
|
Term
| Esophagus - Neural Control of Peristalsis |
|
Definition
Nucleus Ambiguous stimulates progressive ACh driven contractions of proximal striated muscle_x000D_
Parallel Inhibitory and Excitatory innervation of smooth muscle - both vagal_x000D_
Cholinergic excitatory pathways most prominent proximally_x000D_
Noncholinergic inhibitory pathways most prominent distally_x000D_
Results in progressive delay in contractions along esophagus_x000D_ |
|
|
Term
| Esophagus - Lower Esophageal Sphincter Activity |
|
Definition
Tonically closed at rest_x000D_
Pressure falls 2 seconds after swallowing, remains low for 5-6 seconds_x000D_
Allows content emptying into stomach during proximal food peristalsis_x000D_
Pressure increases when peristaltic wave reaches distal esophagus |
|
|
Term
|
Definition
Movement of gastric contents into the esophagus through the Lower Esophageal Sphincter_x000D_
Transient relaxation of LES stimulated by vagal afferents signaling stomach distension _x000D_
Occasional reflux is normal_x000D_
Gastroesophageal Reflux Disease when often enough to cause symptoms or complications |
|
|
Term
| Gastroesophageal Reflux Disease - Pathogenesis |
|
Definition
Transient relaxation of lower esophageal sphincter - milder disease_x000D_
Hiatal hernia traps reflux contents near LES - more severe disease_x000D_
Hypotension of LES - more severe disease_x000D_
Increased duration of esophageal mucosa acidification - impaired emptying and decreased salivation |
|
|
Term
| GERD - Transient Lower Esophageal Sphincter Relaxations (TLSERs) |
|
Definition
Stimulated by vagal afferents signaling stomach distension_x000D_
Responsible for most reflux episodes in patients without hiatal hernias - compared to strain or low LES pressure_x000D_
Less responsible for reflux episodes in patients with hiatal hernias_x000D_
BMI correlated with TLESR frequency - obesity predisposes to reflux |
|
|
Term
| GERD - Factors Affecting Severity and Complications |
|
Definition
Duration of esophageal mucosa acidification (pH <4) and Bile exposure_x000D_
Increased duration correlated with increased incidence of esophagitis and Barrett's_x000D_
Bile exposure particularly important for Complicated Barrett's |
|
|
Term
| GERD - Other Conditions Mimicking GERD Symptoms |
|
Definition
Coronary Artery Disease_x000D_
Gallstones_x000D_
Gastric or esophageal cancer_x000D_
Peptic Ulcer Disease_x000D_
Esophageal motility disorders_x000D_
Pill induced esophagitis_x000D_
Eosinophilic esophagitis |
|
|
Term
|
Definition
Empiric PPI antisecretory trial - evaluate response of symptoms to treatment_x000D_
Endoscopy > Manometry > Reflux Monitoring (pH measurements) _x000D_ |
|
|
Term
| GERD - Esophageal Erosion |
|
Definition
Symptoms do not predict presence or severity of erosive esophagitis_x000D_
Non-erosive reflux disease (NERD) - reflux symptoms without mucosal erosion |
|
|
Term
|
Definition
Proton Pump Inhibitors - must take before food ingestion _x000D_
Histamine Receptor (H2R) Antagonists_x000D_
Laparoscopic Antireflux Surgery - for PPI refractory or intolerant, persistent regurgitation symptoms _x000D_
Lifestyle modifications - weigh loss, avoid precipitating foods |
|
|
Term
| GERD - Long Term Safety Concerns of PPI's |
|
Definition
C. difficile infection_x000D_
Aspiration pneumonia_x000D_
Hip Fracture_x000D_
Fundic Gland Polyps |
|
|
Term
| GERD - Conditions that Decrease LES Tone or Increase Abdominal Pressure |
|
Definition
Alocohol and tobacco_x000D_
Obesity_x000D_
CNS depressants_x000D_
Pregnancy_x000D_
Hiatal hernia_x000D_
Delayed Gastric Emptying / Increased Gastric Volume |
|
|
Term
|
Definition
Esophageal Ulceration_x000D_
Hematemesis, Melena_x000D_
Stricture formation_x000D_
Barrett's Esophagus |
|
|
Term
| Gastric Cell Types- Location and Secretions |
|
Definition
Parietal Cells - Body and Fundus - Acid and intrinsic factor_x000D_
G Cells - Antrum - Gastrin_x000D_
D Cells - entire stomach - Somatostatin_x000D_
ECL Cells - Histamine_x000D_
Chief Cells - Pepsinogen_x000D_ |
|
|
Term
| Peptic Ulcer Disease - Parietal Cell Signal Transduction |
|
Definition
Vagus Nerve --> ACh --> M3 Receptor --> PLC --> Ca increase_x000D_
G Cell --> Gastrin --> Gastrin / CCK Receptor --> PLC --> Ca increase_x000D_
G Cell --> Gastrin --> ECL Cell --> Histamine --> H2 Receptor --> Adenylate Cyclase --> cAMP increase_x000D_
Final common output --> stimulate H/K/ATPase (proton pump) on luminal surface_x000D_
H Efflux, K influx, ATP hydrolysis |
|
|
Term
| Peptic Ulcer Disease - Negative Regulation of Gastric Acid Production |
|
Definition
Low pH --> D Cells in Antrum --> Somatostatin --] G Cell and ECL Cell Inhibition_x000D_
Vagal ACh input not regulated by negative feedback_x000D_
Prostaglandins exert protective negative feedback role |
|
|
Term
| Peptic Ulcer Disease - Normal Gastric Protective Mechanisms |
|
Definition
Prostaglandins (most important) - promote mucous and bicarbonate production and submucosal blood flow_x000D_
Mucous - secreted by neck cells, barrier to H+ back diffusion, traps alkaline secretions, buffers luminal acidity_x000D_
Bicarbonate - secreted into mucous layer, neutralizes acid entering mucous layer_x000D_
Basal membrane and apical tight junctions - barrier function_x000D_
Mucosal blood flow - provides oxygen and nutrients to prevent hypoxia and permit regeneration |
|
|
Term
| Peptic Ulcer Disease - Normal Gastric Damaging Agents |
|
Definition
Acid - Secreted by Parietal Cells_x000D_
Pepsin - Secreted as Pepsinogen by chief cells, activated by low pH_x000D_
Pepsin is reversibly inactivated at pH > 4 - irreversibly inactivated at pH > 6, must be resynthesized _x000D_
Bile - backflow through duodenum into stomach |
|
|
Term
| Peptic Ulcer Disease - Duodenal v Antrum Ulcer Clinical Presentation |
|
Definition
Dudodenal (usually bulb) - pinpoint epigastric burning pain relieved by food ingestion_x000D_
Stomach (usually antrum) - diffuse epigastric pain, nausea, vomiting worsened by food ingestion |
|
|
Term
| Peptic Ulcer Disease - Ulcer Causing Aggressive Agents |
|
Definition
Acid - no acid no ulcer_x000D_
NSAID - local caustic effect and systemic inhibition of prostaglandins via COX-1 inhibition_x000D_
H pylori - increases gastric acid production (duodenal ulcers) and decreases mucosal protection (gastric ulcers)_x000D_
Steroids, smoking, alcohol, bile, caffeine |
|
|
Term
| Peptic Ulcer Disease - Approaches to Medical Treatment |
|
Definition
Inhibit Acid Production - PPI and H2R Antagonists_x000D_
Neutralize Acid - Antacids_x000D_
Treat H pylori_x000D_
Avoid NSAID use_x000D_
Enhance protective mechanisms - sucralfate and misoprostal |
|
|
Term
| Peptic Ulcer Disease - H2 Receptor Antagonists |
|
Definition
Competitive H2R antagonists - high specificity to GI tract_x000D_
Rapid absorption and onset - continuous dosing maintains gastric pH > 4 and inactivates pepsin_x000D_
Hepatic p450 metabolism and renal excretion_x000D_
Rare bradycardia, LFT elevation, anti androgenic effects in men_x000D_
Some potently bind p450 - increases levels of warfarin, phenytoin theophylline, and diazepam |
|
|
Term
| Peptic Ulcer Disease - Proton Pump Inhibitors |
|
Definition
Irreversibly block H/K/ATPase - new pump must be re synthesized to resume acid secretion_x000D_
More effective and longer lasting than H2R Antagonists_x000D_
Delivered as prodrug - must be absorbed systemically to mediate effect_x000D_
Short half life, long duration, hepatic p450 metabolism, minimal drug interactions due to short half life_x000D_
Can increase gastrin production, long use may cause osteoporosis, disrupts normal stomach bacteria |
|
|
Term
| Peptic Ulcer Disease - PPI Delivery and Mechanism of Action |
|
Definition
Delivered as prodrug in acid resistant coating to prevent degradation in stomach _x000D_
Outer layer dissolved by alkaline medium of small intestine - prodrug inactive at neutral pH_x000D_
Absorbed systemically - lipophilic prodrug diffuses across lipid membranes into acidified cellular compartments_x000D_
Enters Parietal cell, protonation traps it inside, becomes concentrated and sulphonated to active drug_x000D_
Drug binds H/K/ATPase and inactivates pump |
|
|
Term
| Peptic Ulcer Disease - Antacids |
|
Definition
Weak bases neutralize HCL to form a salt and H20_x000D_
Temporarily relieve symptoms of dyspepsia_x000D_
Bad taste, may affect absorption of other drugs such as tetracyclines_x000D_
High doses can result in symptoms from excess Mg, Al, and Ca |
|
|
Term
| Peptic Ulcer Disease - Antimicrobial Treatment of H. pylori |
|
Definition
Triple regimens - 2 antibiotics + 1 PPI_x000D_
Ab - Clarithromycin, metronidazole, amoxacillin, tetracycline_x000D_
PPI - omeprazole, peptobismol_x000D_
May add bismuth subsalicyclate to coat ulcer acting as protective layer to prevent further damage |
|
|
Term
| Peptic Ulcer Disease - Medications Enhancing Protective Mechanisms |
|
Definition
Misoprostol - PGE1 analogue - limited use due to bloating, diarrhea, and is an abortifacient_x000D_
Sucralfate - stimulates production of gastric mucous, HCO3, and PGE2_x000D_
Sucralfate may bind other medications in GI lumen - Digoxin, Ciproflaxacin, Theophylline |
|
|
Term
| Zollinger Ellison Syndrome - Overview |
|
Definition
Gastrin secreting tumor - gastrinoma - results in unregulated parietal cell acid secretion_x000D_
Gastrin induces parietal cell hyperplasia, neck cell hyperplasia, mucin hypersecretion_x000D_
Patients present with multiple duodenal ulcers or chronic diarrhea_x000D_
60-90% are malignant - must be identified and removed_x000D_
75% are sporadic solitary tumors - 25% due to Multiple Endocrine Neoplasia 1 |
|
|
Term
|
Definition
Multifocal hyperplasia and neoplasia_x000D_
Pituitary, Parathyroid, and Pancreatic Islets most common_x000D_
Adrenal cortex, lung, and thymus also affected_x000D_
Menin mutation _x000D_
Pancreatic tumors are gastrin secreting tumors - Zollinger Ellison Syndrome - malignancy determines prognosis_x000D_ |
|
|
Term
| Zollinger Ellison Syndrome - Pathophysiology |
|
Definition
Unregulated gastrin production not subject to negative feedback via paracrine somatostatin_x000D_
Induces parietal cell acid secretion and hyperplasia_x000D_
Results in multiple recurrent non-healing peptic ulcers (usually duodenal)_x000D_
Inappropriate Hypergastrinemia - high gastrin secretion in the presence of gastric acid production |
|
|
Term
| Hypergastrinemia - Appropriate and Inappropriate Causes |
|
Definition
Appropriate as normal response to hypo/achlorhydria_x000D_
Normal in setting of PPIs and H2RA, atrophic gastritis, H pylori, chronic renal failure, vagotomy_x000D_
Inapproriate in setting of normal gastric acid secretion_x000D_
Abnormal in ZES, retained antrum syndrome, antrum dominant H pylori, massive intestinal resection_x000D_ |
|
|
Term
|
Definition
Basal Acid Output - nasogastric collection tube for 1 hr overnight, measure volume H+ produced_x000D_
Maximal Acid Output - same measurement after Pentagastrin (synthetic gastrin) stimulation_x000D_
Must stop therapy prior to measurement |
|
|
Term
| Zollinger Ellison Syndrome - When to Suspect in Patients |
|
Definition
Severe PUD - multiple, recurrent, non healing ulcers_x000D_
Diarrhea - due to acid secretion_x000D_
Non NSAID, non H Pylori ulcers_x000D_
MEN 1 patients |
|
|
Term
| Idiopathic Gastric Acid Hypersecretion |
|
Definition
Increased Basal and Maximal Acid Output_x000D_
Increased parietal cell mass, meal stimulated acid output, and 24 hour acid secretory profile_x000D_
Results in Duodenal ulcers_x000D_
May be caused by increased parietal cell sensitivity, basal and meal stimulated hypergastrinemia,_x000D_
somatostatin deficiency, decreased bicarbonate secretion_x000D_
Most due to H pylori infection_x000D_ |
|
|
Term
| Heliobacter pylori - Pathophysiology |
|
Definition
Fecal-oral or oral-oral transmission_x000D_
Urea --(urease)--> ammonia + H20 + CO2 --> ammonium + bicarbonate --> neutralizes acidic environment_x000D_
Flagellae and spiral morphology facilitate penetration of mucous layer_x000D_
Enzyme products - protease and phospholipase - disrupt mucosal barrier_x000D_
Adherence factors permit attachment to surface of mucous cells_x000D_
Chronic active inflammation of gastric mucosa and systemic humoral immune response_x000D_
Interferes with mucous production - does not invade mucosa_x000D_ |
|
|
Term
| Heliobacter pylori - Effects on Gastric Acid Secretion |
|
Definition
Initial decrease in acid secretion - multiple progression pathways_x000D_
Antral predominant infections result in duodenal ulcers - acid hypersecretion_x000D_
Can develop into asymptomatic chronic gastritis - normal acid levels_x000D_
Can result in pangastritis and Gastric ulcers, risk of cancer and lymphoma - acid hyposecretion |
|
|
Term
| Heliobacter pylori - Mechanistic Link to Duodenal Ulcers |
|
Definition
Antral infection inhibits somatostatin production --> unopposed gastrin release_x000D_
Basal and postprandial hypergastrinemia induce gastric acid hypersecretion_x000D_
Duodenal gastric metaplasia permits H pylori colonization of duodenal bulb_x000D_
Local bulb defenses are damaged in setting of acid hypersecretion --> duodenal ulceration_x000D_
Metaplasia occurs at junctional zone between stomach and duodenum |
|
|
Term
| Heliobacter pylori - Spectrum of Infections and Complications |
|
Definition
Chronic Gastritis_x000D_
Duodenal Ulcers (75-90%)_x000D_
Gastric Ulcers (60-70%) - mainly via reduction of mucosal defenses_x000D_
Chronic Gastritis --> atrophy --> intestinal metaplasia --> dysplasia --> cancer_x000D_
MALToma_x000D_
Non Ulcer Dyspepsia |
|
|
Term
| Heliobacter pylori - Risk of Cancer |
|
Definition
Chronic gastritis --> gastric atrophy --> intestinal metaplasia --> dysplasia --> Gastric Antral Cancer_x000D_
MALToma from monoclonal lymphocyte expansion during chronic lymphocytic gastritis _x000D_ |
|
|
Term
| Heliobacter pylori - Infection to Disease Pathways |
|
Definition
Exposure --> Acute Infection --> Superficial Gastritis --> Hyper/Hyposecretory_x000D_
Hypersecretory --> Antral predominant --> Duodenal ulcer_x000D_
Hyposecretory --> Chronic pangastritis --> Chronic Atrophic Gastritis --> Gastric Ulcer or Gastric Cancer (0.05%)_x000D_
Hyposecretory --> Chronic pangastritis --> lymphocytic predominant --> MALToma_x000D_ |
|
|
Term
| Heliobacter pylori - Gastric Cancer |
|
Definition
Infection associated with corpus and antral cancers - not with cardia and GE junction cancers_x000D_
CagA pathogenicity island associated with cancer - toxin directly injures epithelial cells_x000D_
CagA + infections associated with increased cytokine release and inflammation_x000D_
IL-1 host polymorphism increases risk for progressing to pangastritis and developing cancer_x000D_ |
|
|
Term
| Heliobacter pylori - Testing for Infection |
|
Definition
Biopsy mucosa - thiazine stain, ISH, or IHC for pathogen_x000D_
CLO test - biopsy placed in chamber, pH becomes basic with urease activity_x000D_
Blood - test for antibodies, cannot determine active from past infection_x000D_
Breath test - ingest radioactive substrate, measure exhaled radioactive urea |
|
|
Term
| Acute Gastric Ulceration - Morphology |
|
Definition
Sharply demarcated with normal adjacent mucosa_x000D_
Base is stained brown/black by acid digestion of extravasated blood_x000D_
No scarring and thickening of blood vessels that characterize chronic peptic ulcers |
|
|
Term
| Peptic Ulcer Disease - NSAID Induced Mucosal Injury |
|
Definition
Local caustic damage - minor role_x000D_
Systemic COX1 inhibition results in decreased prostaglandin protective activity - major role_x000D_
COX1 inhibition --> reduced mucous and bicarbonate production, decreased blood flow_x000D_
H pylori infection induces COX2 - increases risk of ulceration |
|
|
Term
| Peptic Ulcer Disease - Prevention of Ulcers in NSAID Users |
|
Definition
Misoprostol replaces prostaglandin protection - effective prevention of Gastric Ulcers_x000D_
Omeprazole (PPI) to reduce acid secretion - effective prevention of Gastric and Duodenal Ulcers |
|
|
Term
| Peptic Ulcer Disease - Curling's Ulcer and Cushing's Ulcer |
|
Definition
Curling's - proximal duodenal ulcers seen in burn patients_x000D_
Cushing's - gastric, duodenal, and esophageal ulcers seen in patients with intracranial disease _x000D_
Cushing's Ulcers due to direct stimulation of vagal nuclei - high risk of perforation |
|
|
Term
| Non-Ulcer Dyspepsia - Other Non Ulcer Causes of Epigastric Pain |
|
Definition
GERD, pancreatitis, gallstones_x000D_
Pneumonia, Pulmonary Embolus, Myocardial Infarction, Ruptured Aortic Aneurysm |
|
|
Term
| GI Tract - Active Inflammation |
|
Definition
Indicated by presence of neutrophils above basement membrane contacting epithelial cells_x000D_
May be present in both acute and chronic disease states |
|
|
Term
| Stomach - Gastric Motor Functions |
|
Definition
Fundus and Proximal Body - Storage_x000D_
Distal Body and Antrum - Processing and Emptying_x000D_
Pylorus - Processing and Emptying |
|
|
Term
|
Definition
Increase in gastric volume without a significant increase in intragastric pressure_x000D_
Stomach distension from food ingestion stimulates gastric mechanoreceptors_x000D_
Vago-Vagal reflex through brainstem --> stimulates prolonged gastric relaxation_x000D_
Stomach can accomodate 1-1.5 liters of food when relaxed |
|
|
Term
| Stomach - Gastric Slow Waves |
|
Definition
Interstitial cells of cajal in greater curvature of proximal body serve as pacemaker cells_x000D_
Spontaneous waves 3x/ min - electrical current spreads distally and circumferetially_x000D_
Fasting - few slow waves result in contraction / post prandial - most slow waves trigger contraction |
|
|
Term
| Stomach - Fasting State Gastric Motility |
|
Definition
Cyclical Migrating Motor Complex (MMC) - last 100 min each_x000D_
Phase I - long duration, quiescent, no contractions_x000D_
Phase II - few irregular motor contractions_x000D_
Phase III - 5 min long, regular high amplitude contractions, sweep particles out of stomach - housecleaning_x000D_
Different from postprandial contractions because pylorus remains open to allow emptying of contents_x000D_
Stimulated by Motilin or erythromycin activating Motilin receptors |
|
|
Term
| Stomach - Post Prandial Gastric Motility |
|
Definition
Mixing waves - weak peristaltic contractions stimulated by gastric slow waves_x000D_
Propagates from mid stomach to antrum gathering strength as it travels_x000D_
Pylorus contracts when wave approaches, only small amount of content passes through_x000D_
Retropulsion - content pushed backwards and upstream from closed pylorus towards proximal stomach_x000D_
Allows mixing of food contents with gastric secretions and trituration - reducing particle size |
|
|
Term
| Stomach - Gastric Emptying of Liquids |
|
Definition
Fluid empties at linear rate dependent on antroduodenal pressure gradient_x000D_
Determined by liquid volume and gastric tone_x000D_
Independent of contractile activity |
|
|
Term
| Stomach - Gastric Emptying of Solids |
|
Definition
Ingested food mixed with gastric juices into semi-liquid called chyme_x000D_
Intense peristaltic waves force several millimeters of chyme through pylorus = pyloric pump_x000D_
Increased gastric food content stimulates stomach distension_x000D_
Myenteric nerves in stomach wall respond by stimulating pyloric pump contractions and reducing pyloric tone_x000D_
Food induced gastrin secretion stimulates same neural response |
|
|
Term
| Stomach - Effect of Food Content on Gastric Emptying |
|
Definition
Larger volume empties faster than smaller volume_x000D_
Liquids empty faster than semiliquids that empty faster than solids_x000D_
Carbohydrates empty faster than proteins that empty faster than fat |
|
|
Term
| Stomach - Enterogastric Nervous Reflexes |
|
Definition
Duodenal neural feedback to slow gastric emptying_x000D_
Vagal brainstem loop, enteric nervous connections from duodenum to stomach, and inhibitory sympathetics_x000D_
Enterogastric nervous feedback inhibits pyloric pump and increases pyloric tone_x000D_
Enterogastric nervous reflexes activated by high acid, protein, fat, or volume reaching duodenum_x000D_ |
|
|
Term
| Stomach - Enterogastric Hormonal Feedback |
|
Definition
CCK released by jejunal epithelial cells in response to high fat slows gastric emptying_x000D_
Somatostatin, dopamine, and secretin all exert negative feedback |
|
|
Term
| Gastroparesis - Causes and Symptoms |
|
Definition
Stomach paralysis - impaired transit of food from stomach to duodenum_x000D_
Diabetic, post surgical, medication induced and idiopathic most common causes_x000D_
Can be caused by paraneoplastic, rheumatologic, neurologic, and myopathic syndromes_x000D_
Nausea, vomiting, early satiety - morning nausea_x000D_
Bezoar formation_x000D_ |
|
|
Term
| Gastroparesis - Diagnosis |
|
Definition
Gastric scintigraphy_x000D_
Radiolabelled low fat egg beaters - measure abdominal retention over 1-4 hours |
|
|
Term
| Gastroparesis - Management |
|
Definition
Small, frequent, low fat, low fiber meals_x000D_
Glucose control in diabetic gastroparesis_x000D_
Medications - prokinetic and antiemetic agents_x000D_
Gastric electrical stimulation - high frequency, low energy, short pulse duration stimulation _x000D_
Surgery |
|
|
Term
| Gastroparesis - Metoclopramide |
|
Definition
Prokinetic via DA Antagonism (myenteric plexus), 5 HT4 Agonism, and smooth muscle muscarinic stimulation_x000D_
Antiemetic via central DA and 5 HT3 antagonism_x000D_
Extrapyramidal Parkinsons-like side effects - DA mediated |
|
|
Term
| Gastroparesis - Domperidone |
|
Definition
Prokinetic via DA Antagonism (myenteric plexus), 5 HT4 Agonism, and smooth muscle muscarinic stimulation_x000D_
Antiemetic via central DA and 5 HT3 antagonism_x000D_
Does not cross BBB - no extrapyramidal effects_x000D_
Used in patients that cant tolerate EPS of Metoclopramide or Parkinson's Patients with gastroparesis |
|
|
Term
| Gastroparesis - Erythromycin |
|
Definition
Prokinetic - Binds and activates motilin receptors on GI smooth muscle_x000D_
Used for inpatients_x000D_
Interacts with CYP-3A inhibitors |
|
|
Term
| Gastroparesis - Scopolamine |
|
Definition
Antiemetic - ACh M1 receptor antagonist_x000D_
Administered as path for severe nausea and motion sickness |
|
|
Term
| Gastroparesis - Ondansetron and Granisetron |
|
Definition
| Antiemetic - 5 HT3 antagonists |
|
|
Term
|
Definition
Rapid emptying of hypertonic liquids from stomach into intestine_x000D_
Often occurs in patients with gastrojejunostomy for gastroparesis_x000D_
Early nausea, flushing, diarrhea, and syncope - mediated by release of vasoactive factors _x000D_
Late hypoglycemia - mediated by release of insulin _x000D_ |
|
|
Term
| Non Ulcer Dyspepsia - Overview |
|
Definition
Symptoms referable to upper GI tract not due to structural disease_x000D_
Post prandial distress syndrome - early satiety, bothersome fullness_x000D_
Epigastric pain syndrome - pain and burning |
|
|
Term
| Non Ulcer Dyspepsia - Pathophysiology |
|
Definition
Delayed gastric emptying, poor compliance, ineffective gastric contraction patterns_x000D_
Visceral hypersensitivity to pain_x000D_
Psychological stress and personality traits influence symptoms _x000D_
May be alternative presentation of GERD |
|
|
Term
|
Definition
Reflux - most common_x000D_
Pill - localized caustic injury_x000D_
Allergy - eosinophillic esophagitis_x000D_
Viral - Herpes, CMV_x000D_
Crohns, trauma, radiation_x000D_
Fungal - Candida_x000D_ |
|
|
Term
|
Definition
Allergic response to food antigen - hypersensitivity reaction_x000D_
Increased intraepithelial eosinophils, absence of acid reflux, damage affects entire length of esophagus_x000D_
Circular rings and longitudinal esophageal furrows - trachealization of esophagus_x000D_
Present with dysphagia (difficulty swallowing) and odynophagia (pain with swallowing) - refractory to PPI therapy_x000D_
Common comorbid atopic dermatitis, allergic rhinitis, asthma - uncommon peripheral eosinophilia or high IgE_x000D_
Treat with oral steroids and avoidance of food allergens |
|
|
Term
| Esophagus - Skin Disorders Affecting the Esophagus |
|
Definition
Pemphigus - blistering autoimmune diseases - acantholysis, loss of intercellular adhesions_x000D_
Pemphigoid - blistering autoimmune disease w/o acantholysis_x000D_
Lichenoid Reaction |
|
|
Term
| Dysphagia - Webs and Rings |
|
Definition
Webs - protrusions of mucosa, semicurcumferential eccentric lesions in upper esophagus_x000D_
Schatzki Rings - thick ring containing mucosa, submucosa, and hypertrophic muscularis propria - reflux induced_x000D_
A Rings - above GE junction, squamous mucosa_x000D_
B Rings - at or below GE junction, gastric cardia mucosa |
|
|
Term
|
Definition
Incomplete LES relaxation_x000D_
Increased LES tone_x000D_
Aperistalsis of esophagus_x000D_
Present with difficulty swallowing_x000D_
Food stasis and decay --> risk for squamous cell carcinoma |
|
|
Term
|
Definition
Selective Atrophy (not fibrosis) of inner circular layer of muscularis propria_x000D_
Affects lower esophagus_x000D_
Seen in CREST presentation of Scleraderma |
|
|
Term
|
Definition
Longitudinal tears of esophagus mucosa near GE junction_x000D_
Due to severe retching or vomiting caused by acute alcohol intoxication_x000D_
Failure of esophageal musculature to relax with prolonged vomitting_x000D_
Present as hematemesis, commonly heal completeley |
|
|
Term
| Barrett Esophagus - Pathophysiology |
|
Definition
Intestinal metaplasia of esophageal squamous mucosa as complication of chronic GERD_x000D_
Presence of goblet cells required for diagnosis of intestinal metaplasia and Barrett_x000D_
Increased risk of esophageal adenocarcinoma |
|
|
Term
| Barrett Esophagus - Morphology_x000D_ |
|
Definition
Red velvety mucosa extending upward from GE junction_x000D_
Long segment > 3 cm above GE junction / short segment < 3 cm involved _x000D_
Short v Long length of metaplasia determined at initiation of injury, do not interconvert _x000D_
Greater risk of cancer in long segments_x000D_ |
|
|
Term
| Barrett Esophagus - Histologic Changes |
|
Definition
Intestinal metaplasia - presence of goblet cells_x000D_
Dysplasia - proliferation, atypical mitoses, hyperchromasia, increased N:C ratio, immature epithelial cells_x000D_
Gland architecture dysruption, budding, irregular shapes, cellular crowding_x000D_
High grade dysplasia exhibits more severe cytologic and architectural change_x000D_
Adenocarcinoma - invasion into lamina propria |
|
|
Term
| Esophageal Adenocarcinoma - Pathogenesis |
|
Definition
Stepwise acquisition of genetic changes progressing from dysplasia to invasive cancers_x000D_
Transitions to invasive carcinoma after invading laminae propria _x000D_
Most often occurs in distal third of esophagus adjacent to Barrett esophagus_x000D_
Present with dysphagia, weight loss, hematemesis, chest pain, vomiting_x000D_
Often spreads to submucosal lymphatics at time of diagnosis - poor prognosis |
|
|
Term
| Esophageal Squamous Cell Carcinoma - Pathogenesis_x000D_ |
|
Definition
Affects all portions of esophagus - 50% in middle_x000D_
In situ squamous dysplasia grows into tumor mass - commonly obstructs lumen_x000D_
No relation to reflux - commonly associated with EtOH and tobacco use_x000D_
Invade surrounding structures and spread via local lymph nodes_x000D_
Poor prognosis - advanced stage and large size at detection |
|
|
Term
| Esophageal Squamous Cell Carcinoma - Lymph Node Metastasis |
|
Definition
Circumferential and Longitudinal spread along esophagus_x000D_
Lesions in upper 1/3 spread to cervical LN_x000D_
Lesions in mid 1/3 spread to mediastinal, paratracheal, and tracheobronchial LN_x000D_
Lesions in lower 1/3 spread to gastric and celiac LN_x000D_
Invade surrounding structures - lungs, aorta, mediastinum, pericardium_x000D_
Symptomatic tumors usually large at diagnosis - already invaded esophageal wall and metastasized |
|
|
Term
| GI Disturbances - Red Flags Concerning for Malignancy |
|
Definition
Dysphagia_x000D_
Vomiting with meals, Early Satiety_x000D_
Weight Loss_x000D_
Blood in Stool_x000D_
Age > 45 years |
|
|
Term
| Dyspepsia - Definition and Differential Diagnosis |
|
Definition
Upper abdominal (epigastric) discomfort, usually worse after meals, present for greater than 4 weeks_x000D_
DDx - Peptic Ulcer Disease, Non Ulcer Dyspepsia_x000D_
Atypical presentation for GERD, hepatobiliary disorders, pancreatitis, or non GI disease process |
|
|
Term
| Chronic Gastritis - Etiology_x000D_ |
|
Definition
Helicobacter pylori and Autoimmune Gastritis most common_x000D_
Less often caused by radiation, chronic bile reflux, mechanical injury, systemic disease, amyloidosis |
|
|
Term
|
Definition
Tissue damage associated with eosinophilic infiltrate in mucosa and muscularis_x000D_
Most commonly affects antral or pyloric region_x000D_
Presents with vomiting, abdominal pain, diarrhea (protein losing enteropathy), GI bleeding, ascites_x000D_
Associated with peripheral eosinophilia and elevated serum IgE (opposite of whats seen in Eosinophilic Esophagitis)_x000D_
Allergic reaction most common cause - cow's milk, soy protein_x000D_
Can be cause by drugs or in association with systemic collagen vascular disease |
|
|
Term
| Atrophic Chronic Gastritis - Heliobacter pylori Infection_x000D_ |
|
Definition
Loss of parietal and chief cells from oxyntic mucosa areas (body and fundus)_x000D_
H pylori induced intestinal metaplasia --> cells lack Lewis receptors needed for H pylori binding_x000D_
H pylori can spread up to body and fundus inducing gastritis and cellular damage |
|
|
Term
| Atrophic Chronic Gastritis - Autoimmune Gastritis |
|
Definition
Autoantibodies directed against apical H+ pump or intrinsic factor in parietal cells_x000D_
Self reactive CD4 T cell mediated cell injury_x000D_
Achlorhydria --> Loss of acid --> hypergastrinemia and antral G cell and ECL cell hyperplasia_x000D_
Loss of intrinsic factor --> B12 deficiency --> pernicious anemia_x000D_
Loss of chief cells secondary to gland destruction --> reduced serum pepsinogen levels_x000D_ |
|
|
Term
| Atrophic Gastritis - Definition |
|
Definition
| Loss of parietal and chief cells from oxyntic mucosa areas (body and fundus) |
|
|
Term
| Autoimmune Atrophic Gastritis - Risk of Cancer |
|
Definition
Prolonged hypergastrinemia stimulates ECL cell proliferation_x000D_
Risk of transformation into low grade neuroendocrine carcinoid tumor_x000D_
Intestinal metaplasia (goblet cells) of gastric mucosa --> risk of gastric adenocarcinoma_x000D_
No hypergastrinemia in H pylori mediated atrophic gastritis due to less severe parietal cell loss |
|
|
Term
| Autoimmune Atrophic Gastritis - Effects of Vitamin B12 Deficiency |
|
Definition
Pernicious megaloblastic anemia_x000D_
Atrophic glossitis - tongue becomes smooth and beefy_x000D_
Subacute Combined Systems Degeneration - demyelination, axonal degeneration, neuronal death_x000D_
Paresthesias, numbness, loss of vibration sense and proprioceptions_x000D_
Sensory ataxia, positive Romberg sign, limb weakness, spasticity, Babinski sign_x000D_
Personality changes, memory loss, psychosis |
|
|
Term
| Inflammatory and Hyperplastic Gastric Polyps |
|
Definition
Most common type (75%) of gastric polyps_x000D_
Chronic gastritis initiates injury and reactive hyperplasia leading to polyp growth_x000D_
Most commonly occur in antrum_x000D_
Variable size, single or multiple_x000D_
Small risk of neoplastic transformation, correlated with size |
|
|
Term
|
Definition
Occur sporadically and in patients with Familial Adenomatous Polyposis_x000D_
Increased incidence with PPI therapy --> gastrin stimulated glandular hyperplasia_x000D_
Occur in gastric body and fundus_x000D_
Benign and usually asymptomatic |
|
|
Term
|
Definition
Xanthelasma is a collection of lipid laden macrophages forming a yellowish plaque_x000D_
Not associated with underlying lipid metabolic disorder_x000D_
Can occur anywhere_x000D_
Must distinguish from gastric signet ring cancer |
|
|
Term
| Hypertrophic Gastropathies |
|
Definition
Enlarged gastric rugal folds due to epithelial hyperplasia without inflammation_x000D_
Menetrier disease - foveolar mucous cell hyperplasia due to excessive TGF alpha secretion_x000D_
Zollinger Ellison Syndrome - parietal cell hyperplasia due to gastrin secreting tumor_x000D_ |
|
|
Term
|
Definition
Diffuse hyperplasia of foveolar mucousal epithelial cells_x000D_
Enlarged rugal folds due to epithelial hyperplasia without inflammation (hypertrophic grastropathy)_x000D_
Excessive mucin secretions lost in feces --> protein losing enteropathy --> hypoproteinemia _x000D_
Weight loss, diarrhea, peripheral edema, increased risk of gastric adenocarcinoma _x000D_ |
|
|
Term
| Mucosa Associated Lymphoid Tissue Lymphoma (MALToma) |
|
Definition
Extra Nodal Marginal Zone B Cell Lymphoma_x000D_
Arise at sites of chronic inflammation - most commonly in GI Tract_x000D_
Most often arise in sites normally devoid of organized lymphoid tissue_x000D_
Indolent tumor can transform into aggressive diffuse large B cell lymphoma |
|
|
Term
|
Definition
Chronic inflammation (usually H pylori) drives formation of Gastric MALT_x000D_
MALT can progress to indolent extranodal marginal zone B cell lymphoma_x000D_
Lymphoepithelial lesions distinguish MALToma from chronic gastritis (lymphocytes don't invade epithelium)_x000D_
If associated with H pylori, infectin drives NFkB signaling through MLT and BCL-10 signaling _x000D_
Treat with antibiotics, remove inflammatory stimulus, reduce NFkB signaling --> tumor regression_x000D_
Translocations constituitively activating MLT and BCL-10 drive tumor progression_x000D_ |
|
|
Term
|
Definition
Usually occur in background of chronic atrophic gastritis with intestinal metaplasia_x000D_
Composed of intestinal type columnar epithelial cells_x000D_
Represent dysplastic lesion - risk of adenocarcinoma correlated to size of lesion |
|
|
Term
| Diffuse Gastric Adenocarcinoma - Genetic Mutations |
|
Definition
CDH1 / E Cadherin mutations in familial and 50% of sporadic forms_x000D_
Loss of function through mutation or promoter methylation is key step in cancer development_x000D_
CDH1 mutation also common in lobular breast carcinoma_x000D_
BRCA2 mutation carriers at increased risk of diffuse gastric cancer |
|
|
Term
| Intestinal Type Gastric Adenocarcinoma - Genetic Mutations |
|
Definition
Increased risk in patients with FAP - APC mutation_x000D_
Mutations in beta catenin and mismatch repair genes seen_x000D_
Classic dysplasia --> carcinoma sequence of progression_x000D_
Genetic alterations resemble those seen in colon adenocarcinoma |
|
|
Term
| Diffuse Gastric Adenocarcinoma - Morphology and Histology |
|
Definition
Infiltrative growth of small clusters of cells into mucosa and stomach wall_x000D_
Discohesive cells, do not form glands_x000D_
Large mucin vacuoles --> push nuclei to side --> signet ring cytology_x000D_
Evoke desmoplastic reaction, stiffen gastric wall --> linitis plastica |
|
|
Term
| Intestinal Type Gastric Adenocarcinoma - Morphology and Histology |
|
Definition
Most commonly involve lesser curvature of antrum_x000D_
Bulky tumors composed of glandular structures_x000D_
Grow in broad cohesive fronts, form exophytic mass or an ulcerated tumor_x000D_
May present as non-healing ulcer_x000D_
Contain apical mucin vacuole_x000D_ |
|
|
Term
| Gastric Adenocarcinoma - Signs and Symptoms |
|
Definition
Early - dyspepsia, dysphagia, nausea - resemble chronic gastritis_x000D_
Late - weight loss, anorexia, altered bowel habits, anemia, hemorrhage |
|
|
Term
| Intestinal Obstruction - Clinical Manifestations |
|
Definition
Abdominal pain and distension, vomiting, constipation_x000D_
80% of mechanical obstructions due to hernias, adhesions, intususceptions, and volvulus_x000D_
10-15% of mechanical obstructions due to tumors and infarctions_x000D_
Most common in Esophagus, Duodenum, and Small Intestine - rare in colon, stomach, and anus_x000D_ |
|
|
Term
| Tracheo-esophageal fistula - Clinical Manifestations |
|
Definition
90% have blind upper esophageal segment and fistula b/w lower esophagus and trachea_x000D_
Presents with aspiration, regurgitation, and respiratory distress_x000D_
Absence of GI gas pattern on X rays_x000D_
Often associated with other anatomic congenital anomalies |
|
|
Term
| Duodenal Stenosis - Clinical Manifestations |
|
Definition
Vomiting beginning at birth - bilious if stenosis is distal to Ampulla of Vater_x000D_
Most occur in proximal portion near Ampulla_x000D_
Most due to a web - failure of lumen recanalization - or due to annular pancrease_x000D_
Double bubble sign on radiographs - gas pocket in stomach and dilated duodenum proximal to occlusion |
|
|
Term
| Small Intestineal Atresia - Clinical Manifestations |
|
Definition
85% are single sites - 15% are multiple_x000D_
Usually due to intrauterine vascular accidents or known post natal vascular accidents_x000D_
Classified based on if blind ends are connected and if there is a defect in associated mesentery |
|
|
Term
| Anorectal Atresia - Clinical Manifestations |
|
Definition
Manifest with abnormal perineum and imperforate anus_x000D_
Classified as above or below levator sling_x000D_
Associated with fistula to the bladder, urethra, or vagina_x000D_
Infant fails to pass meconium within first 48 hours - components ingested in utero |
|
|
Term
| Short Bowel Syndrome - Clinical Manifestations |
|
Definition
Loss of bowel surface and absorptive area_x000D_
Decreased fluid and electrolyte reabsorption, nutrient and bile salt deficiency, chronic diarrhea_x000D_
Requires Total Parenteral Nutrition - can lead to chronic liver disease_x000D_
Common indication for bowel transplantation in children |
|
|
Term
| Gastrointestinal Cysts - Duplications |
|
Definition
Intestinal duplication located on mesenteric border -shares common wall with GI lumen - does not communicate_x000D_
Most frequent in distal ileum - can occur anywhere in GI tract - location determines clinical manifestation_x000D_
Can be tubular or cystic - cystic duplications are larger and create mass compressive symptoms_x000D_ |
|
|
Term
| Gastrointestinal Cysts - Neurenteric Remnants |
|
Definition
Originate from dorsal midline GI tract - attach or pass through vertebrae and spinal cord_x000D_
Most frequent in cervical and lumbar areas_x000D_
Dorsal cutaneous are of hypertrichosis or hyperpigmentation_x000D_
Present as GI obstruction, respiratory distress, CNS paralysis and infection |
|
|
Term
|
Definition
Failure of neural crest cell migration or survival to form enteric nervous system_x000D_
Lack of neural relaxation signals results in tonic contraction_x000D_
Hirschprung - congenital, neonatal presentation with failure to pass meconium and abdominal distension_x000D_
Acquired - Chagas disease destroys enteric nervous system cells |
|
|
Term
| Necrotizing Enterocolitis |
|
Definition
Most common GI Emergency in newborns - associated with prematurity_x000D_
Onset associated with enteral feeding - may introduce pathogen - initiate inflammatory cycle_x000D_
Cycle of mucosal barrier breakdown, transmural invasion of gut bacteria, inflammation --> mucosal damage_x000D_
Can cause ischemia, coagulative necrosis - progress to sepsis and shock_x000D_
Presents within first 2 weeks post natal with bloody stool, abdominal distension, apnea, and circulatory collapse_x000D_
Pneumatosis intestinalis - gas within bowel wall on radiographs_x000D_
Most frequently in terminal ileum, cecum, ascending colon - can affect any segment_x000D_
Post NEC stricture formation from fibrosis or short bowel syndrome from resection_x000D_ |
|
|
Term
| Intestinal Intussusception |
|
Definition
Invagination of one intestinal segment into distal segment_x000D_
Intussusceptum invaginates into intussuscipiens_x000D_
Intestine relatively unteathered in childhood_x000D_
Repeatedly invaginates and recovers - multiple episodes of pain and resolution_x000D_
Can result in obstruction of lumen, compression of mesenteric vessels, and segment ischemia and infarction |
|
|
Term
| Cystic Fibrosis - GI Manifestations |
|
Definition
CFTR functions to secrete Cl - mutations decrease water secretion --> thick mucous_x000D_
Meconium ileus - obstruction of lumen by viscid meconium plug - may rupture causing peritonitis_x000D_
Loss of exocrine pancreas function, recurrent pancreatitis_x000D_
Chronic hepatic disease, focal biliary or multilobar cirrhosis_x000D_
Nutritional failure to thrive, hypoporeteinemia, edema, deficiencies of fat soluble vitamins (ADEK) |
|
|
Term
|
Definition
Occurs in Fed State_x000D_
Gradient of peristaltic contraction rates to mix luminal contents and increase contact time with epithelium_x000D_
Increased frequency of segmenting contractions in duodenum > jejunum > ileum_x000D_
Driven by pacemaker cells_x000D_
Regulated by intrinsic reflex arcs, extrinsic neural input, and stimulated by postprandial gastrin release |
|
|
Term
| Bowel - Migrating Motor Complex |
|
Definition
Occurs in fasting state_x000D_
Sequential, organized, short peristaltic waves starting in stomach and progressing caudally_x000D_
Initiated by motilin secretion from terminal ileum - stopped by gastrin release with next meal_x000D_
House keeping function - takes 100-150 min to reach terminal ileum |
|
|
Term
| Small Intestine - Secretions |
|
Definition
1.5 Liters of water and mucous per day - total volume of 9-10 liters passes through per day_x000D_
Mucous lubricates lumen and protects cells - water needed for enzymatic nutrient hydrolysis_x000D_
Driven by Cl- secretion from apical CFTR in epithelial crypts - regulated by cAMP |
|
|
Term
| Small Intestine - Surface Epithelium Structure and Function |
|
Definition
Villi - absorption _x000D_
Crypts - secretion |
|
|
Term
| Digestion - Carbohydrates |
|
Definition
Salivary amylase initiates digestion of polysaccharides into disaccharides _x000D_
Pancreatic amylase secreted into duodenum continues digestion_x000D_
Polysaccharides --> Disaccharides --> Monosaccharides via brush border disaccharidases_x000D_
Cotransport of monosaccharides with Na into enterocytes_x000D_
Majority of glucose absorption occurs in Jejunum - lactose absorption variable due to genetic differences |
|
|
Term
|
Definition
Initiated in stomach by HCl and Pepsin - continued in duodenum by pancreatic proenzyme activation_x000D_
Trypsinogen --(Enterokinase)--> Trypsin_x000D_
Other zymogen proteases and trypsinogen --(Trypsin) --> active proteases and trypsin_x000D_
Brush border aminopeptidases finalize digestion to single amino acids_x000D_
Cotransport of AA with Na through neutral, basic, and acidic AA transporters_x000D_
Cotransport of di and tripeptides with H+ _x000D_
Absorption occurs throughout jejunum and ileum |
|
|
Term
| Digestion - Fat Digestion and Emulsification |
|
Definition
Digestion initiated in stomach by gastric lipase - TG --> FA and diglycerides (DG)_x000D_
Stable emulsion with inner TG, DG, cholesterol, vitamins and outer phospholipids, MG, FA, and bile salts_x000D_
Digestion in duodenum by pancreatic lipase - TG --> FA and monoglycerides (MG)_x000D_
Colipase secreted by pancreas facilitates TG interaction with lipase_x000D_
Phospholipase A2 secreted by pancreas digests phospholipids on emulsion and anchors lipase to emulsion_x000D_
No digestion by brush border enzymes on enterocytes_x000D_ |
|
|
Term
| Digestion - Absorption of Lipid Products_x000D_ |
|
Definition
Products of lipid digestion solubulized into micelles - core MG, FFA, cholesterol with surrounding bile salts_x000D_
Micelles diffuse to apical brush border of enterocytes and release lipids_x000D_
Lipids diffuse into cells down concentration gradient - reesterified inside cell to form original products_x000D_
Lipids packaged with apoproteins into chylomicrons - exocytosed from basolateral domain_x000D_
Chylomicrons enter lacteals (lymphatic capillaries) - enter systemic circulation via throacic duct_x000D_
Bile salts remain in lumen - absorbed by distal ileum_x000D_ |
|
|
Term
|
Definition
Not digested - absorbed intact_x000D_
Water soluble - simple diffusion or carrier mediated - B complex, C_x000D_
Fat soluble - absorbed via micelles - ADEK_x000D_
B12 - bound by IF from gastric parietal cells, absorbed as complex in terminal ileum via specific transporter |
|
|
Term
|
Definition
Produced by microorganisms - large amounts in animal products, absent in plant products_x000D_
Ingested bound to binding proteins _x000D_
Gastric acid and pepsin releases B12 from binding proteins - binds salivary carrier R protein_x000D_
Pancreatic proteases release B12 from R protein in duodenum_x000D_
Parietal cells produce intrinsic factor - binds B12 and carries to terminal ileum_x000D_
IF-B12 absorbed in terminal ileum via IF receptors_x000D_
Transferred to transcobalamin II - delivers to liver, bone marrow, GI tract, and dividing cells in body |
|
|
Term
| GI Disease Affecting Vitamin B12 Absorption |
|
Definition
Acid Hyposecretion - PPI therapy - can't liberate B12 from binding proteins in food_x000D_
Pancreatic insufficiency - chronic pancreatitis - can't liberate B12 from R binding protein_x000D_
Crohn's Disease or Terminal Ileum disease or resection - can't bind and absorb B12 bound to IF_x000D_
Autoimmune Gastritis - Destruction of Parietal Cells - no production of IF |
|
|
Term
| GI Disease Affecting Iron Absorption |
|
Definition
Acid Hyposecretion - PPI therapy - acid required for conversion of ferric to absorbable ferros iron _x000D_
IBD / Celiacs - sloughing of enterocytes, loss of ferritin, impaired absorption |
|
|
Term
| GI Disease Affecting Calcium Status |
|
Definition
Lactose intolerance - decreased absorption due to loss of brush border enzymes_x000D_
Celiac and Crohn Disease - decreased absorption due to enterocyte damage |
|
|
Term
| Small Intestine - Fluid Absorption |
|
Definition
9-10 Liters per day pass through - all but 1.5 liters per day absorbed_x000D_
Absorption rate in Ileum > Jejunum > Duodenum_x000D_
Basolateral Na/K/ATPase pump Na into blood, bring K in_x000D_
Multiple Apical NaCl transporters bring NaCl into cell _x000D_
Water follows NaCl osmotically into cell through water permeable epithelium - NO CONCENTRATING |
|
|
Term
|
Definition
Salt and water absorption - iso osmotic - NO CONCENTRATING_x000D_
Waste storage_x000D_
No digestive function or nutrient absorption - no brush border |
|
|
Term
|
Definition
One way valve regulates entry of material from ileum into colon _x000D_
Opens with ileal distension - closes on cecum contraction - prevents backflow of colonic bacteria and contents_x000D_
Ileal brake - fat sensors inhibit gastric motility - mediated by Peptide YY |
|
|
Term
| Colon - Motility and Absorption |
|
Definition
Poor Motility --> Increased Absorption --> Hard Feces --> Constipation_x000D_
Excess Motility --> Decreased Absorption --> Loose Feces --> Diarrhea |
|
|
Term
| Colon - Absorption and Secretion |
|
Definition
Surface cells absorb Na and Cl, secrete K and HCO3_x000D_
Crypt cells secrete Cl in cAMP dependent pathway_x000D_
1.5 L pass through per day - absorbs 1.4 L per day --> 100 ml per day in feces_x000D_
Iso osmotic absorption - NO CONCENTRATING _x000D_
Limited capacity compared to small intestine - easily overwhelmed resulting in diarrhea |
|
|
Term
| Colon - Motility Patterns |
|
Definition
Segmentation - slow (2/hr), regulated by autonomic nervous system_x000D_
Propulsive - weak peristaltic waves stimulated by intrinsic nerves_x000D_
Gastrocolic reflex - gastrin released after meal stimulates strong contractions in proximal colon to move contents |
|
|
Term
|
Definition
Faculative and obligate anaerobes _x000D_
Slow flow promotes bacterial growth_x000D_
Produce Short Chain Fatty Acids - direct nourishment for colonic epithelial cells_x000D_
Produce gas, vitamin K, stimulate immune development and IgA secretion_x000D_
Endogenous flora compete against pathogenic flora _x000D_ |
|
|
Term
|
Definition
Holding - contraction of puborectalis and external anal sphincter_x000D_
Skeletal response - relaxation of PR and EAS, contraction of levator ani, rectus and diaphragm muscles_x000D_
Smooth response - relaxation of internal anal sphincter, contraction of rectal muscles_x000D_
CNS control in hypothalamus - local reflex arc from fecal distension of rectum |
|
|
Term
| Collateral Circulation in Small Intestine v Colon |
|
Definition
Colic arteries connected by marginal artery - rich collateral circulation_x000D_
Small intestine supplied by parallel arcade system - no collateral circulation_x000D_
Segmental infarct more common in small intestine_x000D_
Can tolerate slowly progressive loss of blood supply from single artery_x000D_ |
|
|
Term
|
Definition
Fibrotic bands forming at sites of inappropriate adhesion of GI tract to abdominal wall_x000D_
May serve as rotation points resulting in obstruction and ischemia |
|
|
Term
| Ischemic Bowel Disease - Mucosal v Transmural Infarction_x000D_ |
|
Definition
Mucosal - can involve any segment of GI tract, segmental, patchy, ulcerated hemorrhagic mucosa_x000D_
Bowel wall thickened by edema (thumb printing), no serosal hemorrhage or serositis_x000D_
Caused by acute or chronic hypoperfusion_x000D_
Transmural - watershed zones most susceptible, splenic flexure most common_x000D_
Sharply demarcated, congested, coagulative necrosis, perforation, serositis_x000D_
Caused by acute arterial obstruction |
|
|
Term
| Ischemic Bowel Disease - Pathogenesis |
|
Definition
Initial hypoxic injury - minimal damage, epithelial cells resistant to transient hypoxia_x000D_
Reperfusion injury - majority of damage_x000D_
Damage due to free radical production, neutrophil infiltration, inflammatory mediators (complement and TNF)_x000D_
Mucosa most sensitive - inflammatory and necrotic changes begin at surface and progress through wall layers |
|
|
Term
| Ischemic Bowel Disease - Clinical Features |
|
Definition
Acute transmural infarction presents with sudden severe abdominal pain, nausea, vomiting, bloody diarrhea_x000D_
Can progress to shock and vascular collapse from blood loss - sepsis from bacteria crossing damaged barrier_x000D_
Loss of peristaltic sounds, abdominal rigidity from muscle spasms_x000D_
Symptoms overlap with acute appendicitis, perforated ulcer, and acute cholecystitis |
|
|
Term
| Ischemic Bowel Disease - Possible Etiologies |
|
Definition
Atherosclerosis, aortic aneurysm, hypercoagulable states, oral contraceptive use --> thromboembolism_x000D_
Cardiac failure, shock, dehydration, vasoconstrictive drugs --> hypoperfusion_x000D_
Systemic vasculitis, polyarteritis nodosum, wegner granulomatosis_x000D_
Mesenteric venous thrombosis, sigmoid volvulus |
|
|
Term
| Crohns Disease - Overview |
|
Definition
Can affect any GI segment - relative sparing of rectum - discontinuous skip lesions_x000D_
Transmural inflammation - fistulae and stricture formation_x000D_
Extraintestinal manifestations_x000D_
Increased risk of carcinoma in inflammed areas_x000D_
Microscopic granulomas, fibrosis, cryptitis, and knife like ulcerations_x000D_
Significant genetic link - NOD2 |
|
|
Term
| Crohns Disease - Genetic Predisposition |
|
Definition
Significant genetic associations to disease phenotype_x000D_
NOD2 polymorphism identified_x000D_
NOD2 binds intracellular bacterial peptidoglycans (LPS) resulting in NFkB activation_x000D_
Defective NOD2 may prevent clearance of intracellular bacteria or result in impaired inflammatory regulation_x000D_
Mutations associated with Crohns are in Leucine Rich Repeats involved in LPS binding |
|
|
Term
| Crohns Disease - Morphology _x000D_ |
|
Definition
Skip lesions - multiple sharply delineated lesions anywhere along GI tract_x000D_
Aphthous lesion - occur over lymphoid aggregates, may coalesce into linear ulcers on mesenteric side_x000D_
Cobblestone mucosa - ulceration alternating with normal mucosa, edema_x000D_
Creeping fat - mesenteric fat extends around serosal surface_x000D_
Transmural inflammation - knife like fissures, fibrosis, stricture and fistulae formation_x000D_
Hypertrophy of muscularis propria --> stricture formation_x000D_ |
|
|
Term
| Crohns Disease - Endoscopic Findings |
|
Definition
Ileitis - stenosis, linear ulceration, mucopurulent exudate - loss of normal nodularity_x000D_
Deep fissures, cobblestoning, segmental lesions, rectal sparing |
|
|
Term
| Crohns Disease - Histology |
|
Definition
Neutrophil infiltration through damaged epithelial barrier (cryptitis) cluster into crypt abscesses --> crypt destruction_x000D_
Distortion of mucosal architecture due to repeated crypt damage and regeneration_x000D_
Epithelial metaplasia --> gastric antral like glands or Paneth cell metaplasia in left colon_x000D_
Noncaseating granulomas, cutaneous granuloma nodules |
|
|
Term
| Crohns Disease - Clinical Presentation |
|
Definition
Intermittent attacks of mild diarrhea, fever, and abdominal pain - interrupted by asymptomatic periods_x000D_
Weight loss, growth failure, perianal disease_x000D_
May mimic acute appendicitis or bowel perforation_x000D_
Physical or emotional stress or cigarette smoking may trigger reactivation_x000D_
Extraintestinal manifestations _x000D_
Increased risk of colonic adenocarcinoma |
|
|
Term
| Crohns Disease - Oral Manifestations |
|
Definition
Oral lesions - may be initial presentation_x000D_
Persistent and painless enlargement of lips - fissures and cracking_x000D_
Anguluar chylitis, atrophic glossitis_x000D_
Linear ulcerations deep in tissue folds of oral mucosa_x000D_
Non caseating granulomas |
|
|
Term
| Inflammatory Bowel Disease - Clinical Presentation in Adults v Children |
|
Definition
CD - Children most often present as colitis - growth failure is major feature - more inflammatory disease than adults_x000D_
UC - Children more frequently present with pancolitis or limited disease that progresses to extensive disease |
|
|
Term
| Inflammatory Bowel Disease - Extraintestinal Manifestations |
|
Definition
Uveitis, migratory polyarthritis, sacroiliitis, ankylosing spondylitis - CD and UC_x000D_
Pericholangitis and primary sclerosing cholangitis - CD and UC_x000D_
Erythema nodosum, clubbing of fingertips - CD only |
|
|
Term
| Ulcerative Colitis - Overview |
|
Definition
Limited to Colon - starts distal, progresses proximally_x000D_
Inflammation limited to mucosa_x000D_
Extraintestinal manifestations_x000D_
Increased risk of carcinoma in inflammed areas_x000D_
Cryptitis, crypt abscesses, crypt distortion - no granulomas or strictures_x000D_
Less significant genetic link than CD |
|
|
Term
| Ulcerative Colitis - Morphology |
|
Definition
Continuous lesion from rectum extending proximally_x000D_
Pancolitis - entire colon / Left sided colitis - transverse colon / Ulcerative proctitis - limited distal disease_x000D_
Sparing of small intestine except for backwash ileitis in pancolitis_x000D_
Broad based ulcers alinged on long access, mucosal atrophy and loss of normal folds_x000D_
Pseudopolyps - islands of regenerating mucosa_x000D_
No mural thickening or stricture formation_x000D_ |
|
|
Term
| Ulcerative Colitis - Endoscopic Findings |
|
Definition
Loss of vascular pattern_x000D_
Granularity_x000D_
Exudates_x000D_
Diffuse continuous disease |
|
|
Term
| Ulcerative Colitis - Histology |
|
Definition
Neutrophil infiltration through damaged epithelial barrier (cryptitits) cluster into crypt abscesses _x000D_
crypt destruction and distortion_x000D_
Epithelial metaplasia_x000D_
Diffuse inflammatory process limited to mucosa_x000D_
No granulomas |
|
|
Term
| Ulcerative Colitis - Clinical Presentation |
|
Definition
Attacks of bloody diarrhea with stringy mucoid material, lower abdominal pain, cramps_x000D_
Pain temporarily relieved by defecation_x000D_
Relapsing disorder - physical or emotional stress or smoking cessation may trigger reactivation_x000D_
Extraintestinal manifestations_x000D_
Increased risk of colonic adenocarcinoma |
|
|
Term
| Ulcerative Colitis - Risk of Cancer |
|
Definition
Increased risk of colorectal adenocarcinoma with increased duration of disease and inflammation_x000D_
High grade flat dysplasia, dysplasia associated lesion or mass, primary sclerosing cholangitis increase risk |
|
|
Term
| Ulcerative Colitis - Oral Manifestations |
|
Definition
Ulcerations of oral mucosa_x000D_
Angular cheilitis due to nutritional deficiencies |
|
|
Term
| IBD - Symptomatic Treatment |
|
Definition
Limit diarrhea and maintain hydration_x000D_
Opioid mu receptor agonists - reduce intestinal motility, increase colonic transit time_x000D_ |
|
|
Term
| IBD - Aminosalicyclates Mechanism of Action_x000D_ |
|
Definition
Aspirin + Amino group_x000D_
Reduces formation of prostaglandins and leukotrienes_x000D_
Inhibits NFkB activity, inhibits NK cells, mucosal lymphocytes and macrophages_x000D_
Scavenges reactive oxygen species_x000D_
Functions locally at GI epithelial cells - formulated to prevent systemic absorption in small intestine_x000D_ |
|
|
Term
| IBD - Indications for Aminosalicyclate Therapy |
|
Definition
Mild to moderately active ulcerative proctoclitis or crohns disease_x000D_
Maintenance of disease remission |
|
|
Term
| IBD - Aminosalicyclate Administration and Delivery Options |
|
Definition
AZO Compound - 5 ASA coupled to inert compound bound by AZO bond _x000D_
Activity of 5-ASA dependent on cleavage of AZO bond by colonic bacteria_x000D_
Limited use for small intestine inflammation of Crohns_x000D_
Mesalamine Compound - 5 ASA monomer inside carrier complex_x000D_
Formulated for targeted release (time, pH) in small intestine or other site_x000D_ |
|
|
Term
|
Definition
AZO compound - 5 ASA coupled to sulfapuridine by AZO bond_x000D_
Oral admin - activation of 5 ASA dependent on AZO bond cleavage by colonic bacteria_x000D_
Limited use for small intestine inflammation of Crohns_x000D_
Dyspepsia, nausea, headache, anoerxia side effects due to sulfapuridine |
|
|
Term
|
Definition
AZO compound - 5 ASA Dimer bound by AZO bond_x000D_
Oral admin - activation of 5 ASA dependent on AZO bond cleavage by colonic bacteria_x000D_
Limited use for small intestine inflammation of Crohns_x000D_
No sulfonamide --> reduced toxicity_x000D_ |
|
|
Term
|
Definition
AZO compound - 5 ASA bound with 4 ABA by AZO bond_x000D_
Oral admin - activation of 5 ASA dependent on AZO bond cleavage by colonic bacteria_x000D_
Limited use for small intestine inflammation of Crohns_x000D_
No sulfonamide --> reduced toxicity_x000D_ |
|
|
Term
|
Definition
Mesalamine compound - 5 ASA inside ethylcellulose microgranule_x000D_
Oral admin - formulated for timed release in small intestine - no need for colonic bacteria activation_x000D_
Able to target small intestine affected by Crohns_x000D_
No sulfonamide --> reduced toxicity |
|
|
Term
|
Definition
Mesalamine compound - 5 ASA inside pH sensitive resin_x000D_
Oral admin - formulated to release at pH >7 - targets distal ileum and proximal colon_x000D_
No sulfonamide --> reduced toxicity |
|
|
Term
|
Definition
Mesalamine compound - 5 ASA monomer_x000D_
Enema (Rowasa) or suppository (Cenasa) admin_x000D_
Effective for sigmoid colitis and proctitis_x000D_
No sulfonamide --> reduced toxicity |
|
|
Term
| IBD - Corticosteroid Mechanism of Action |
|
Definition
Antinflammatory effects to reduce T cell inflammatory response in intestine_x000D_
Reduce formation of inflammatory cytokines - TNFa, IL 1, IL 6_x000D_
Inhibit transcription of NFkB, PLA2, and COX2_x000D_
If make wrong diagnosis miss infectious etiology - corticosteroids will inhibit the immune response and hurt patient_x000D_ |
|
|
Term
|
Definition
ASA effective to treat mild to moderately active ulcerative disease_x000D_
ASA effective to maintenance of disease remission_x000D_
Corticosteroids effective to induce disease remission |
|
|
Term
| IBD - Corticosteroid Administration and Delivery Options |
|
Definition
Oral - Prednisone_x000D_
Oral controlled release - budesonide_x000D_
IV - hydrocortisone, methylprednisone_x000D_
Enema - hydrocortisone - effective for left sided ulcerative colitis |
|
|
Term
| IBD - Corticosteroid Toxicity |
|
Definition
Common toxic side effects seen with chronic use_x000D_
Myopathy, osteonecrosis, osteoporosis_x000D_
Fluid retention, hyperglycemia, weight gain, hypokalemia, hyperlipidemia, growth failure_x000D_
Dyspepsia, ulceration_x000D_
Depression, anxiety, psychosis_x000D_
Cataracts, glaucoma, skin manifestations |
|
|
Term
| IBD - Immunosuppressive Purine Antimetabolites _x000D_ |
|
Definition
Azathioprine, 6 mercaptopurine, Methotrexate _x000D_
Inhibit DNA synthesis in rapidly dividing inflammatory lymphocytes_x000D_ |
|
|
Term
| IBD - Cyclosporine and Tacrolimus |
|
Definition
Prevents translocation and nuclear import of NFAT subunit_x000D_
NFAT regulates transcription of IL 2, GM CSF, TNFa, and IFNg in T cells_x000D_
Inhibits lymphocyte function systemically and in intestinal mucosa_x000D_
Absorbed systemically --> systemic effect |
|
|
Term
|
Definition
Monoclonal antibody against TNFa_x000D_
Blocks T cell inflammatory response_x000D_
IV admin - systemic effect_x000D_
Antibodies against the drug may develop and inhibit effect_x000D_
Must be hospitalized during therapy to prevent complication of infection_x000D_ |
|
|
Term
|
Definition
Monoclonal IgG4 antibody against integrin a4 subunit_x000D_
Prevents leukocyte binding to vascular adhesion molecules and migration into inflamed tissue_x000D_
Complication of reactivation of JC virus resulting in multifocal leukoencephalopathy_x000D_
Limited use for refractory patients only |
|
|
Term
| Celiac Disease - Overview |
|
Definition
Malabsorptive diarrhea affecting proximal small bowel - may present as iron deficiency anemia_x000D_
Immune response generated against Gliadin after gluten ingestion --> tissue damage_x000D_
Villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis_x000D_
Auto antibodies generated against gliadin, tissue transglutaminase, and endomysium_x000D_
Responds to gluten free diet_x000D_
Diagnosis made on clinico-pathologic correlation |
|
|
Term
| Celiac Disease - Pathogenesis |
|
Definition
Gliaden peptides induce expression of IL-15 by epithelial cells --> activate intraepithelial CD8 T lymphocytes_x000D_
Cytotoxic CD8 T lymphocytes induced to express NKG2D - kill epithelial cells expressing ligand MIC-A_x000D_
Epithelial damage allows gliadin peptides to cross barrier --> damidated by tissue transglutaminase (tTG)_x000D_
Deamidated gliaden peptides presented by CD4 Th1 cells by APC --> IFNg production and B cell clonal activation_x000D_
Gliaden specific CD4 T cells / anti gliadin, tTG, and endomysium B cell antibodies / non specific CD8 T cells |
|
|
Term
| Celiac Disease - Morphology and Histology |
|
Definition
Most severe in 2nd portion of duodenum and proximal jejunum _x000D_
Intraepithelial CD8 T lymphocytosis, villous atrophy, crypt hyperplasia --> malabsorption_x000D_
Increased plasma cells, mast cells, and eosinophils in lamina propria_x000D_
CD8 T cells in epithelium, CD4 T cells in lamina propria_x000D_
No linear correlation b/w severity of mucosal damage and clinical symptoms_x000D_ |
|
|
Term
| Celiac Disease - Suggestive Endoscopic Findings |
|
Definition
Scalloped appearance along duodenal folds_x000D_
Mucosal nodularity |
|
|
Term
| Celiac Disease - Clinical Presentation |
|
Definition
Adults - anemia, diarrhea, bloating, fatigue_x000D_
Pediatric - irritability, abdominal distention, anorexia, diarrhea, failure to thrive, weight loss, muscle wasting_x000D_
Extraintestnal arthritis, seizure disorders, apthous stomatitis, iron deficiency anemia, pubertal delay, short stature_x000D_
Long term increased risk of anemia, female infertility, osteoporosis, and cancer |
|
|
Term
| Celiac Disease - Serology Tests |
|
Definition
IgA anti Tissue Transglutaminase (TTG) - highly sensitive and specific_x000D_
IgA anti Endomysium (EMA) - highly sensitive and specific_x000D_
IgA and IgG anti Gliadin - less sensitive and specific_x000D_
Many patients with Celiacs are also IgA deficient - may need to test IgG TTG to confirm negative test result |
|
|
Term
| Celiac Disease - Diagnosis |
|
Definition
Characteristic morphologic abnormalties in small bowel of patient ingesting gluten_x000D_
+/- presence of serum AGA, EMA, or TTG antibodies_x000D_
Clinical remission while on gluten free diet is gold standard |
|
|
Term
| Celiac Disease - Latent and Silent |
|
Definition
Latent - positive serology, no mucosal abnormalities, signs or symptoms_x000D_
Silent - positive serology, mucosal damage and loss of villi, but no signs or symptoms |
|
|
Term
| Celiac Disease - Genetics |
|
Definition
Strong HLA association_x000D_
90% of patients have HLA DQ2 (only 30% of controls)_x000D_
Most of remainder have HLA DQ8_x000D_
10% have affected 1st degree relative |
|
|
Term
| Celiac Disease - Oral Manifestations |
|
Definition
Ulceartions of oral mucosa_x000D_
Enamel pitting - indicates enamel hypoplasia |
|
|
Term
| Microscopic Colitis - Collagenous and Lymphocytic Colitis_x000D_ |
|
Definition
Present with chronic, non bloody, watery diarrhea without weight loss_x000D_
Grossly normal appearance - normal radiographic and endoscopic studies_x000D_
Collagenous - dense subepithelial collagen layer, intraepithelial lymphocytes, mixed inflammatory infiltrate_x000D_
Lymphocytic - normal subeithelial collagen, greater increase of intraepithelial lymphocytes, associated with Celiacs |
|
|
Term
|
Definition
Eosinophilic infiltrate of superficial mucosa - patchy_x000D_
Neutrophilic cryptitis and no architectural distortion --> acute and active process_x000D_
Presents with blood streaked stool usually before age 1, diarrhea, abdominal pain - normal appearance and weight_x000D_
Fecal leukocytes, mild peripheral eosinophilia, rare hypoalbuminemia or anemia_x000D_
Often triggered by cows milk or soy milk - removing trigger allows clinical and symptomatic resolution_x000D_
Usually able to reintroduce trigger food later in life_x000D_ |
|
|
Term
| GI Radiology - Mucosal v Submucosal Lesions |
|
Definition
Mucosal Lesions - nodular, granular, ulcerated surface_x000D_
Submucosal lesions - smooth surface, abrupt angles to luminal contour_x000D_
Extrinsic lesions - broad based, smooth tethered folds |
|
|
Term
|
Definition
Fungal infection of esophageal mucosa_x000D_
Increased risk with esophageal obstruction, abnormal motility, or immunosuppression (AIDS)_x000D_
Presents with dysphagia and retrosternal pain_x000D_
Multiple, small confluent ovoid plaques separated by normal mucosa and pseudomembrane formation |
|
|
Term
| Small Esophageal Ulcers - Differential Diagnosis |
|
Definition
Herpes Type I esophagitis_x000D_
Drug induced - tetracyclines, NSAIDs, KCl, Quinidine, Alendronate sodium_x000D_
Reflux |
|
|
Term
|
Definition
Thick lobulated edges seen in squamous cell carcinoma and adeonocarcinoma, drug induced, Barretts, or TB_x000D_
Central portion of lesion destroys blood supply, becomes necrotic and ulcerates --> inflammatory reaction_x000D_
Thin edge indicates no central lesion pathology or minimal reaction to pathology - HIV, CMV |
|
|
Term
| Distal Esophageal Stricture - Radiology Differential Diagnosis |
|
Definition
Long Smooth - reflux esophagitis, nasogastric intubation, ZES, alkaline reflux_x000D_
Short Smooth - reflux esophagitis, Barrett_x000D_
Irregular Surface - squamous cell carcinoma, adenocarcinoma, carcinoma of cardia_x000D_
Schatzki Ring - reflux induced stricture_x000D_
Abnormal beak like appearance - Achalasia |
|
|
Term
|
Definition
Spontaneous esophageal perforation_x000D_
Sudden rapid increase in intraluminal pressure_x000D_
Most often caused by wretching and vomiting after EtOH ingestion_x000D_
Vertically oriented transmural tear of distal esophagus |
|
|
Term
| GI Radiology - Benign v Malignant Ulcers |
|
Definition
Benign - hole protrudes outward from contour, thin overhanging edge, smooth straight radiating folds_x000D_
Malignant - mass effect, mucosal nodularity, clubbed nodular pointed folds radiate to irregular edge of ulcer |
|
|
Term
| Focal Gastric Mucosal Nodularity - Differential Diagnosis |
|
Definition
Lyphoid hyperplasia secondary to H. pylori gastritis_x000D_
Gastric metaplasia_x000D_
Early gastric carcinoma_x000D_
MALT Lymphoma_x000D_
Normally shows polygonal shaped tufts separated by shallow grooves --> areae gastricae_x000D_ |
|
|
Term
| Gastric Polyps - Differential Diagnosis |
|
Definition
Solitary Mucosal - hyperplastic polyp, fundic gland polyp, rare adenoma_x000D_
Multiple Mucosal - hyperplastic polyp, fundic gland polyp, FAP, PJ Hamartomas, Juvenile polyposis_x000D_
Solitary Submucosal - GI stromal tumor, Lipoma, Hemangioma, Neurofibroma, Granular Cell tumor, Lymphoma_x000D_
Multiple Submucosal - Lymphoma or Metastatic cancer |
|
|
Term
|
Definition
Protein calorie malnutrition characterized by energy deficiency_x000D_
Wasting of muscle and fat - loss of adipose from buttocks and thighs_x000D_
Preservation of visceral and serum proteins_x000D_
Caused by inadequate intake of calories and protein |
|
|
Term
|
Definition
Acute protein calorie malnutrition characterized by edema and enlarged fatty liver_x000D_
Sufficient calorie intake and energy stores - insufficient protein consumption_x000D_
Edema - pedal edema, distended abdomen_x000D_
"the sickness the baby gets when the new baby comes" - weened off protein rich breast milk |
|
|
Term
| Gastroparesis - Nutritional Therapy |
|
Definition
Maintain hydration, small frequent meals, low fat and low fiber to avoid delaying gastric emptying_x000D_
Risk of developing electrolyte, vitamin, and mineral deficiencies |
|
|
Term
| Inflammatory Bowel Disease - Nutritional Therapy |
|
Definition
Elemental diet - partially digested components increase absorption_x000D_
Parenteral nutritional support to let bowel recover_x000D_
Risk of developing electrolyte, vitamin, and mineral deficiencies |
|
|
Term
| Celiac Disease - Nutritional Therapy |
|
Definition
Gluten free diet - eliminate wheat, rye, and barley_x000D_
May suffer from secondary lactose intolerance form loss of brush border enzymes_x000D_
Risk of developing electrolyte, vitamin, and mineral deficiencies |
|
|
Term
| Malabosorption - Phases of Nutrient Absorption |
|
Definition
Intraluminal digestion - macromolecules broken down into smaller components_x000D_
Terminal digestion - brush border enzyme digestion of nutrients into monosaccharides and amino acids_x000D_
Transepithelial transport - fluid, nutrients, and electrolytes transported form GI lumen into enterocyte_x000D_
Lymphatic transport - absorbed lipids transported to lymphatics |
|
|
Term
|
Definition
290 mOsm - gut cannot concentrate fluid, stool osmolality must always equal blood osmolality_x000D_
NaCl and KCl most abundant solutes in stool - 2(Na+K) + other solutes = 290 mOsm_x000D_
Normal gap of <50 mOsm between 2(Na+K) and 290_x000D_
Increased Osm gap indicates presence of other soluble substances in stool - Mg laxative, undigested lactose_x000D_
If stool Osm measured to be less than 290 --> dilute solution has been added to stool_x000D_ |
|
|
Term
| Diarrhea - Secretory v Malabsorptive |
|
Definition
Secretory - isotonic stool, occurs at all times, persists during fasting_x000D_
Malabsorptive - follows meals, relieved by fasting, associated with steatorrhea |
|
|
Term
| Diarrhea - Watery v Bloody |
|
Definition
Injury to mucosa causing ulceration may cause bloody diarrhea_x000D_
Exudative diarrhea due to inflammatory damage characterized by bloody, purulent stool that persists with fasting_x000D_
E. Coli O157 and Shigella cause bloody diarrhea_x000D_
C. difficile releases toxins inducing mucin secretion, increasing stool osmolality resulting in watery diarrhea_x000D_
Damage to absorptive surface colon cells with normal secretive crypt cells --> secretory watery diarrhea_x000D_ |
|
|
Term
| Melanosis Coli - Brown Bowel |
|
Definition
Caused by use of certain laxatives that stimulate motility and speed transit_x000D_
Surface epithelial damage impairs ability to absorb water_x000D_
Melanin like pigment accumulates in lamina propria macrophages_x000D_
Colon may appear brown on endoscopy |
|
|
Term
| Diarrhea - Vibrio cholerae |
|
Definition
Severe watery "rice water" diarrhea_x000D_
Up to 1 liter lost per hour - dehydration, hypotension, muscular cramping, anuria, shock, death_x000D_
Flagellar proteins attach to enterocytes - hemaglutinin mediates detachment and shedding in stool_x000D_
Preformed toxin - B subunit binds GM1 ganglioside inducing endocytosis and retrograde transport to ER_x000D_
A subunit escapes degradation - ADP ribosylates and activates Gs --> adenylate cyclase --> cAMP_x000D_
cAMP opens CFTR channel --> Cl secretion --> Na, HCO3, and H20 secretion --> massive diarrhea |
|
|
Term
|
Definition
Bloody diarrhea - fever and abdominal pain_x000D_
Low infective dose - resistant to acidic degradation in stomach_x000D_
Taken up by M cells over Payers patches - escape into laminae propria - engulfed by macrophages_x000D_
Induce apoptosis in macrophages --> inflammatory response damages epithelial barrier_x000D_
Shigella in lumen invade enterocytes via basolateral membrane or inject proteins via type III secretion system |
|
|
Term
| Diarrhea - Enterohemorrhagic E. Coli O157:H7 |
|
Definition
Bloody diarrhea and hemolytic uremic syndrome_x000D_
Produce shiga-like toxins |
|
|
Term
| Diarrhea - Enterotoxigenic E. Coli |
|
Definition
Secretory, noninflammatory watery diarrhea - traveler's diarrhea_x000D_
LT - heat labile toxin - activates adenylate cyclase --> cAMP --> Cl secretion_x000D_
ST - heat stable toxin - activates guanylate cyclase --> gAMP --> electrolyte secretion |
|
|
Term
| Diarrhea - Clostridium difficile - Pseudomembranous Colitis |
|
Definition
Watery diarrhea - fever, leukocytosis, abdominal pain, cramps, hypoalbuminemia_x000D_
Toxins released cause ribosylation of GTPases including Rho_x000D_
Induces disruption of cytoskeleton, tight junction barrier loss, cytokine release, and apoptosis |
|
|
Term
| Diarrhea - Neuroendocrine Tumors |
|
Definition
Vasoactive Intestinal Polypeptide (VIP) secreting tumors stimulate water efflux into gut lumen_x000D_
Gastrinomas increase acid entering duodenum, may inactivate pancreatic enzymes and impair digestion |
|
|
Term
|
Definition
Large volume diarrhea indicates pathology in small intestine_x000D_
Small intestine responsible for majority of fluid absorption_x000D_
Small volume diarrhea indicates small intestine is functional - pathology must be in colon |
|
|
Term
|
Definition
Chronic relapsing abdominal pain, bloating, and changes in bowel habits - most often constipation_x000D_
Pain relieved with defecation, onset associated with change in stool form and frequency_x000D_
Elevated baseline and postprandial sigmoid motility - can reduce with anticholinergic medications_x000D_
Normal gross and microscopic appearance - clinical diagnosis_x000D_
Impairment of brain-gut signaling - decreased modulation of incoming pain signals by frontal and limbic cortex_x000D_
Related to psychologic stressors, diet, abnormal GI motility, and heightened visceral sensitivity_x000D_
Comorbid chronic pain, fibromyalgia, lethargy, depression - must rule out colon cancer and IBD |
|
|
Term
| Irritable Bowel Syndrome - Therapy |
|
Definition
Diet, stress reduction, psychologic therapy_x000D_
Diarrhea - bulking agents, antispasmodics, antidiarrheals_x000D_
Constipation - bulking agents, laxatives, asses pelvic floor function_x000D_
Tricyclic antidepressants and SSRIs may be effective_x000D_ |
|
|
Term
|
Definition
Paradoxic Puborectalis Syndrome - functional outlet obstruction constipation _x000D_
External anal sphincter and puborectalis muscle are abnormally recruited when attempting to defecate_x000D_
Patient contracts muscles when trying to relax_x000D_
Correct with EMG based biofeedback unit_x000D_ |
|
|
Term
|
Definition
Colonic glandular mucosa - endodermal origin - above pectinate line_x000D_
Anal squamous mucosa - ectodermal origin - below pectinate line_x000D_
Anal canal includes 2 centimeters of glandular mucosa above pectinate line _x000D_
Anal canal lymphatics drain to inguinal lymph nodes - rectal lymphatics drain to mesenteric and periaortic nodes |
|
|
Term
| Anal Canal - Epithelial Layer |
|
Definition
External skin identified by adenexal structures (sweat glands) underneath epithelium_x000D_
External anal canal lined by keratinized squamous epithelium w/o underlying adnexal structures_x000D_
Epithelium loses keratinization proximally in anal canal |
|
|
Term
| Anal Canal - Differences Above and Below Pectinate Line |
|
Definition
Below - ectoderm, stratified squamous, inferior rectal artery, inferior rectal vein into systemic circulation_x000D_
Lymphatics drain to inguinal nodes (includes 2cm above pectinate line)_x000D_
Inferior rectal somatic nerves, good sensation_x000D_
Squamous cell carcinoma, external hemorrhoids_x000D_
Above - endoderm, simple columnar, superior rectal artery, superior rectal vein into portal circulation_x000D_
Lymphatics drain to pelvic and lumbar nodes (starting 2 cm above pectinate line)_x000D_
Visceral autonomic innervation, poor sensation_x000D_
Adenocarcinoma, internal hemorrhoids |
|
|
Term
| Anal Canal - Anal Fissures |
|
Definition
| Tears occurring along dentate line - may become infected |
|
|
Term
| Anal Canal - Hypertrophied Anal Papillae |
|
Definition
Surface squamous epithelium with underlying fibrovascular core_x000D_
No malignant potential or clinical consequences_x000D_
Occurs most frequently on dentate line |
|
|
Term
|
Definition
Thin walled, dilated, submucosal vessels protruding beneath anal or rectal mucosa_x000D_
Internal - superior hemorrhoidal plexus - above pectinate line_x000D_
External - inferior hemorrhoidal plexus - below pectinate line_x000D_
Dilated collaterals connecting portal and caval venous systems form due to elevated venous pressure_x000D_
Increased plexus pressure from constipation, pregnancy, portal hypertension_x000D_
Subject to trauma, inflammation, thrombosis, and prolapse _x000D_ |
|
|
Term
| Anal Canal - Malignant Tumors |
|
Definition
Squamous cell carcinoma from lower 1/3, glandular carcinoma from upper 1/3_x000D_
Non keratinizing basaloid appearing tumors from transitional middle 1/3_x000D_
Most frequent are SCC associated with HPV infection and condyloma accuminatum precursor lesion_x000D_
Progress through dysplasia sequence leading to in situ cancer and carcinoma - choiliocyte cells observed_x000D_
HPV E6 inhibits p53 , HPV E7 inhibits RB --> drive cell cycle progression, inhibit DNA repair_x000D_
Staging tumor invasion determines prognosis - different criteria for anal canal and rectal tumors_x000D_ |
|
|
Term
| Anal Canal - Extramammary Paget's Disease |
|
Definition
Adenocarcinoma presenting as growth of single cells in squamous epithelium of anal canal_x000D_
No dysplasia sequence or precursor lesion_x000D_
May spread to peri anal skin resulting in itching and erythema |
|
|
Term
| Gastric Bypass Surgery - Most Common Complications |
|
Definition
Iron and B12 deficiency_x000D_
Stricture at anastamoses |
|
|
Term
| Sleeve Gastrectomy - Mechanism of Action |
|
Definition
Restrictive - reduce volume_x000D_
Remove majority of cells producing ghrelin - normally induces appetite and feeding |
|
|
Term
| Diverticulum - True v False |
|
Definition
True - all layers of luminal wall present_x000D_
False - not all layers present, frequently just mucosa |
|
|
Term
| Diverticulum - Formation of False Diverticuli |
|
Definition
Weak point created where blood vessels penetrate lumen wall at juncture of tenia coli and underlying muscle_x000D_
Increased intraluminal pressure results in compensatory hypertrophy of muscularis propria_x000D_
Hypertrophied muscle generates more intraluminal pressure --> cyclical_x000D_
Mucosa bulges into the weak point of the wall_x000D_
No diverticulum formation in areas lacking tenia coli and weak points - no diverticlum in rectum |
|
|
Term
| Diverticulum - Complications |
|
Definition
Diverticulosis = Massive GI bleed - trauma to mucosa erodes into underlying artery - always bleeds INTO lumen_x000D_
Diverticulitis = inflammation _x000D_
Ischemia from increased pressure in enclosed space - bacterial stasis, entry into mucosa, fecolith trapping_x000D_
Inflammation, abscess formation, peritonitis if bacteria penetrate mucosa_x000D_
Fistulae and stricture formation from inflammation, wall thickening_x000D_ |
|
|
Term
| Diverticulum - Diverticuli in Small Bowel |
|
Definition
Meckle's - True - congenital remnant of vitelline duct connecting yolk sac to embryo GI tract_x000D_
May have ectopic pancreatic and gastric tissue_x000D_
Acquired - True - scleraderma, myopathies - conditions weaken muscle creating hollow visceral myopathies_x000D_
Complications secondary to bacterial overgrowth_x000D_ |
|
|
Term
| Diverticulum - Diverticuli in Esophagus |
|
Definition
Pseudo-diverticuli - inflammation causes dilation of submucosal salivary ducts - not actually diverticuli_x000D_
Zenkers - True - abnormal motility function results in herniation, seen in elderly patients _x000D_
Food can lodge in Zenkers, causing halitosis and increased risk of squamous cell carcinoma |
|
|
Term
|
Definition
Normal true diverticulum of the cecum - contains all layers of GI wall_x000D_
Lined by colonic type mucosa_x000D_
Has tenia coli - can get diverticuli disease |
|
|
Term
| Acute Appendicitis - Pathogenesis |
|
Definition
Increased intraluminal pressure compromises venous outflow - obstruction by fecoltih, gallstone_x000D_
Impaired venous outflow --> edema and arterial compromise --> ischemic injury_x000D_
Stasis of luminal contents --> bacterial proliferation --> inflammatory response_x000D_
Neutrophilic infiltration of muscularis propria_x000D_
Hemorrhagic ulceration, gangrenous necrosis extending to serosa --> rupture and suppurative peritonitis |
|
|
Term
| Acute Appendicitis - Etiology |
|
Definition
Obstruction _x000D_
Infection - parasites_x000D_
Ulcerative colitis and Crohns Disease_x000D_
Endometriosis_x000D_
Drugs - Kayexalate used in renal failure, may cause GI ulceration_x000D_
Radiation - damages proliferating cells at base of crypts |
|
|
Term
|
Definition
Carcinoid - most common, rarely metastasizes_x000D_
Epithelial - mucinous cystadenoma, mucinous cystadenocarcinoma, adenocarcinoma_x000D_
Pseudomyxomatous Peritonei - mucin accumulation in abdomen due to mucin producing tumor_x000D_
Lymphoma - large B cell, rare_x000D_ |
|
|
Term
|
Definition
Any abnormal reaction to a food or food additive_x000D_
Intolerance - non immune mediated_x000D_
Food allergy - immune mediated_x000D_ |
|
|
Term
| Food Allergy - Immediate Clinical Manifestations |
|
Definition
Cutaneous - hives, swollen lips and tongue - occurs in 88% of cases_x000D_
GI - nausea, vomiting, diarrhea, abdominal pain_x000D_
Respiratory - runny nose, sneezing, congestion, cough, wheeze_x000D_
Multiorgan - neurologic and cardio manifestations |
|
|
Term
|
Definition
Epinephrine - EpiPen_x000D_
Alpha Receptors - vasoconstriction, increased blood pressure, decreased capillary leak_x000D_
Beta Receptors - relax bronchial smooth muscle, increase heart rate and cardiac contractility |
|
|
Term
| Food Allergy - Factors that Promote Allergenicity_x000D_ |
|
Definition
Small size - molecular weight <70kd_x000D_
Glycosylation_x000D_
Resistance to thermal or chemical degradation - antacid therapy may increase allergies_x000D_
Linear epitope_x000D_
Solubility in water |
|
|
Term
| Food Allergy - GI Immune System Activity |
|
Definition
Mucous and secretory IgA inhibit absorption of 98% of luminal antigens _x000D_
Antigens taken up by epithelial dendritic cell processes or by M cells and delivered to underlying dendritic cells _x000D_
Dendritic cells can induce Tr1 cells or T reg cells - balance between tolerance and activation_x000D_
Normal response to GI antigen presentation is tolerance |
|
|
Term
| Food Allergy - Oral Tolerance Antigen Administration |
|
Definition
Low dose repeated exposure activates regulatory T cells_x000D_
Single high dose induces anergy in reactive lymphocytes |
|
|
Term
| Food Allergy - Regulatory T Cells |
|
Definition
Th3 - produce TGFb --> directs IgA switch, reduces delayed hypersensitivity reactions_x000D_
Tr1 - secrete IL-10, involved in developing oral tolerance_x000D_
CD4 CD25 T - Foxp3 T reg cells- |
|
|
Term
| Food Allergy - Anaphylaxis Mechanism |
|
Definition
First exposure - antigen is presented to Th2 cells - does not need to occur through oral GI exposure_x000D_
Th2 --(IL4)--> IgE switch in B cells --> food antigen specific IgE secreted --> Fc portion binds to mast cells_x000D_
Th2 --(IL3,IL5)--> Eosinophil recruitment_x000D_
Next exposure - antigen binds and cross links IgE bound to Mast cells_x000D_
Mast cells release inflammatory mediators and activate eosinophils _x000D_ |
|
|
Term
| Colorectal Adenocarcinoma - Cell of Origin |
|
Definition
2 independent genetic hits in the same cell required for dysplasia and carcinoma_x000D_
Likely to occur in dividing but long lived stem cell compartment |
|
|
Term
| Colorectal Adenocarcinoma - Wnt Signaling |
|
Definition
Wnt signaling normally drives proliferation at base of crypt_x000D_
Wnt binding stimulates b-catenin signaling --> C myc and cell proliferation\_x000D_
Mutations in APC lead to unregulated b-catenin signaling and cell proliferation_x000D_
APC mutations found in 85% of sporadic colon cancers_x000D_
APC mutations lead to dysplasia and adenoma - additional mutations required for invasive carcinoma _x000D_ |
|
|
Term
| Colorectal Adenocarcinoma - DNA Repair Pathway |
|
Definition
DNA mismatch repair mechanism is defective in 10% of sporadic cases_x000D_
Recognition, excision, and patching of error mediated by MSH2 and MLH1_x000D_
Mismatch errors occur during DNA synthesis and most often at di and tri nucleotide repeats_x000D_
Incorrect mismatch repair can alter coding region of genes |
|
|
Term
| Colorectal Adenocarcinoma - KRAS |
|
Definition
GTP binding protein - normally activated as downstream target of growth factor receptor activation_x000D_
Active K ras activates RAF/MEK/MAP kinase pathway _x000D_
Activating mutations result in constitutive growth signal_x000D_
Found at higher frequency in large adenomas and invasive cancer_x000D_
Late mutation in chromosomal instability pathway - not mutated in mircosatellite instability pathway |
|
|
Term
| Colorectal Adenocarcinoma - COX2 |
|
Definition
Inducible form - generates PGE2 --> promotes epithelial proliferation_x000D_
Increased expression in colorectal adenocarcinomas_x000D_
NSAIDs suggested to have protective effect_x000D_
COX2 inhibition prevents tumor growth in animal models |
|
|
Term
| Colorectal Adenocarcinoma - Dysplastic Histology |
|
Definition
Nuclear hyperchromasia, elongation, and stratification, high N:C_x000D_
Large nucleoli, eosinophilic cytoplasm, and reduction in goblet cells _x000D_
Failure of epithelial cell maturation during migration from crypt to surface_x000D_
Grade of dysplasia not relevant to prognosis - low grade can progress directly to invasive_x000D_
Defined as invasive when invades submucosa of colon to gain access to lymphatics_x000D_ |
|
|
Term
| Colorectal Adenocarcinoma - Dietary Risk Factors |
|
Definition
High fat, low fiber diet - decreased stool bulk and altered composition of endogenous flora_x000D_
Increased production of oxidative bacterial products - deficiencies in vitamin antioxidants _x000D_
High fat intake promotes increased bile acid secretion - converted into carcinogens by intestinal bacteria |
|
|
Term
| Colorectal Adenocarcinoma - Location_x000D_ |
|
Definition
| Adenomas and adenocarcinomas most frequently occur in sigmoid and left colon |
|
|
Term
| Colorectal Adenocarcinoma - Prognosis |
|
Definition
Prognosis based degree of wall invasion and lymph node metastases_x000D_
A - limited to wall - 80 to 90% 5 year survival_x000D_
B - through wall - 60 to 70%_x000D_
C - lymph node mets - 10 to 30% |
|
|
Term
| Colorectal Adenocarcinoma - Chromosomal Instability Pathway |
|
Definition
Early mutation in APC leads to adenoma formation - sporadic or familial_x000D_
Late mutations of SMAD2/4 and KRAS promote cell growth_x000D_
p53 lost by chromosomal deletion late in progression_x000D_
Telomerase expression increases with tumor progression\ |
|
|
Term
| Colorectal Adenocarcinoma - Microsatellite Instability Pathway |
|
Definition
Early mutation in DNA Mismatch Repair enzymes - MLH1 and MSH2_x000D_
Accumulation of mutations in di and tri nucleotide repeats (microsatellites) _x000D_
Mutations of tumor suppressors BAX TGFb Receptor promoters, activating mutations of BRAF_x000D_
Mutations of KRAS and p53 not seen_x000D_
Frequently affects right colon - more common in sessile serrated adenomas_x000D_
Carcinomas often have prominent mucinous differentiation and peritumoral lymphocytic infiltrates_x000D_ |
|
|
Term
| Colorectal Adenocarcinoma - Right v Left Sided Characteristics |
|
Definition
Right - polypoid exophytic masses extending along one wall, rarely cause obstruction_x000D_
Present with fatigue and weakness due to iron deficiency anemia_x000D_
Left - annular constricting lesions, possible obstruction_x000D_
Present with occult bleeding, changes in bowel habits, or cramping LLQ discomfort_x000D_ |
|
|
Term
| Colorectal Adenocarcinoma - Metastasis |
|
Definition
Liver is most common site_x000D_
May be seen in regional lymph nodes, lungs, and bones_x000D_
Rectal adenocarcinomas drain to inguinal lymph nodes, do not spread to Liver |
|
|
Term
| Colon Polyp - Hyperplastic Polyp |
|
Definition
Most common small epithelial polyp - smooth nodular protrusion_x000D_
Mature goblet and absorptive cells - no dysplasia, no malignant potential_x000D_
Clonal expansion associated with KRAS mutations_x000D_
Result from decreased cell turnover and delayed shedding leading to piling up of cells_x000D_
Must be distinguished from sessile serated adenoma_x000D_
May occur as non specific reaction to adjacent or underlying mass or inflammatory lesion |
|
|
Term
| Colon Polyp - Benign Lymphoid Aggregate |
|
Definition
Normal lymphoid aggregates underlying mucosa_x000D_
Hypertrophy under inflammatory stimulus_x000D_
Protrusion of overlying mucosa into lumen_x000D_
No malignant potential |
|
|
Term
| Colon Polyp - Juvenile Polyp |
|
Definition
Hamartomatous polyp - focal malformations of mucosal epithelium and lamina propria_x000D_
Smooth, pedunculated, cystic central space, dilated glands filled with mucin and inflammatory debris_x000D_
Present with rectal bleeding +/- prolapse_x000D_
No dysplasia, no malignant potential of single polyp_x000D_
Juvenile polyposis - 100's of juvenile polyps, small proportion have dysplsia, increased risk of adenocarcinoma |
|
|
Term
|
Definition
Autosomal dominant syndrome resulting in development of many juvenile colon polyps_x000D_
Can have up to 100 hamartomatous polyps - can cause severe bleeding_x000D_
Associated with mutations in TGFb signaling - SMAD4, BMPR1A_x000D_
Dysplasia occurs in small proportion - increased risk of adenocarcinoma_x000D_
Extraintestinal manifestations - pulmonary arteriovenous malformations |
|
|
Term
|
Definition
| Tumor like growths composed to mature tissues normally present at the site in which the develop |
|
|
Term
| Colon Polyp - Inflammatory Polyp |
|
Definition
Result from chronic cycles of injury, inflammation, and healing_x000D_
Seen in ulcerative colitis, crohn's, and solitary rectal ulcer syndrome_x000D_
No dysplasia, no cysts |
|
|
Term
| Colon Polyp - Peutz Jegher Polyp |
|
Definition
Hamartomatous polyp - large, pedunculated, arborizing network of smooth muscle with non dysplastic epithelium_x000D_
No epithelial dysplasia - no malignant potential of single polyp_x000D_
Poly can serve as traction point to initiate intussusception_x000D_
Peutz Jegher syndrome - multiple PJ polyps, increased risk of cancer |
|
|
Term
|
Definition
Autosomal dominant - multiple GI hamartomatous polyps and mucocutaneous hyperpigmentation_x000D_
Multiple PJ polyps - arborizing network of smooth muscle with non dysplastic overlying epithelium_x000D_
Dark blue/brown macules around mouth, eyes, nostrils, buccal mucosa, hands, genetalia, and perianal region_x000D_
Freckles on fingers and toes is specific for PJS - increased melanin deposition, not melanocyte hyperplasia_x000D_
Increased risk of cancer of colon, pancreas, breats, lung, ovaries, uterus, and testicles - 95% lifetime risk_x000D_
GI adenocarcinomas develop independently of PJ poly - PJ polyps are not precursor lesions_x000D_
Germline mutation in LKB1/STK11 - regulates cell polarization and growth - post natal loss of heterozygosity |
|
|
Term
| Familial Adenomatous Polyposis - Overview_x000D_ |
|
Definition
Autosomal dominant germ line mutation in APC - loss of heterozygosity results in colon adenomas_x000D_
Patients develop 100s of polyps - 100% chance of adenocarcinoma if untreated_x000D_
Prophylactic colectomy - still at risk of neoplasia at ampulla of Vater and stomach_x000D_
Gardner's variant - osteoma of mandible, skull, epidermoid cysts, desmoid and thyroid tumors, supernumary teeth_x000D_
Turcot variant - tumors of CNS, medulloblastomas |
|
|
Term
| Familial Adenomatous Polyposis - Extraintestinal Manifestations |
|
Definition
Adenocarcinoma of duodenum near ampulla of vater and of stomach despite colectomy_x000D_
CHRPE - Congenital Hypertrophy of Retinal Pigment Epithelium _x000D_
Gardner's variant - osteoma of mandible, skull, epidermoid cysts, desmoid and thyroid tumors, supernumary teeth_x000D_
Turcot variant - tumors of CNS, medulloblastomas |
|
|
Term
| Familial Adenomatous Polyposis - Genetics |
|
Definition
Inherited or sporadic g (30%) germline mutation of APC gene _x000D_
Post natal loss of heterozygosity leads to adenoma formation - unregulated Wnt signaling drives proliferation_x000D_
Classic FAP - truncating proteins in middle of gene_x000D_
Attenuated FAP - mutations limited to 3' or 5' of gene result in delayed development of polyps and adenocarcinomas_x000D_
CHRPE requires mutation distal to exon 9 |
|
|
Term
| Hereditary Non Polyposis Colon Cancer - Overview |
|
Definition
Autosomal dominant germ line mutation of DNA mismatch repair genes - MSH2 and MLH1 most common_x000D_
Loss of heterozygosity through mutation or methylation silencing_x000D_
Accumulation of mutations at di and tri nucleotide repeats - microsatellite instability_x000D_
Develop cancer earlier than sporadic, most commonly in right colon_x000D_
Fordyce granules - ectopic secaceous glands in oral mucosa _x000D_
Increased risk of cancer in breast, endometrium, stomach, ovary, ureters, brain, skin, and hepatobiliary tract |
|
|
Term
| Carcinoid Tumors of the Bowel |
|
Definition
Epithelial tumors derived from mucosal endocrine cells_x000D_
Most common in appendix and terminal ileum - location correlates with malignant potential_x000D_
Appendiceal carcinoids rarely metastasize, rectal are usually benign, small intestine are more malignant_x000D_
Appendiceal tumors >2cm and goblet cell carcinoid tumors may be malignant_x000D_
Carcinoid Syndrome - hormonal secretion by metastatic tumor in liver - flushing, diarrhea |
|
|
Term
| Carcinoid Tumors - Overview |
|
Definition
Well differentiated epithelial tumors derived from mucosal endocrine cells_x000D_
IHC positive for synaptophysin, chromogranin, and CD56_x000D_
Majority found in GI - terminal ileum and intestine most common - also affect lungs_x000D_
Secrete hormones - ZES, Carcinoid Syndrome_x000D_
Variable metastatic and malignant potential |
|
|
Term
| Carcinoid Tumors - Carcinoid Sydrome |
|
Definition
Caused by carcinoid tumor secreting serotonin into systemic circulation_x000D_
Cutaneous flushing, diarrhea, sweating, bronchospasm, colickly abdominal pain, right sided cardiac vulvar fibrosis_x000D_
Originate as ileal tumors - metastasize to gain access to systemic circulation - commonly liver_x000D_
Presence of Carcinoid Syndrome indicates metastasis to Liver |
|
|
Term
| Carcinoid Tumors - Metastatic Potential |
|
Definition
Foregut - rarely metastasize_x000D_
Midgut - often multiple and more aggressive, deeper invasive, increased size, necrosis, and mitosis_x000D_
Hindgut - usually benign, rectal rarely metastasize, proximal colon are rare but more metastatic |
|
|
Term
| Malabsorption - Major Causes |
|
Definition
Impaired mechanical digestion - poor dentition, gastrectomy, gastroparesis, vagotomy_x000D_
Impaired chemical digestion - enzyme insufficiency, cystic fibrosis or pancreatic insufficiency_x000D_
Impaired solubilization - insufficient bile salt secretion_x000D_
Impaired absorption - short bowel syndrome, celiacs, impaired fatty acid esterification or chylomicron synthesis |
|
|
Term
| Malabsorption - Carbohydrate |
|
Definition
Carbohydrate malabsorption causes osmotic diarrhea_x000D_
Most common cases are lactose intolerance - lactase deficient_x000D_
Presents with bloating, abdominal cramps, and diarrhea |
|
|
Term
|
Definition
Steatorrhea - excessive fat loss in stool_x000D_
Weight loss, muscle wasting, failure to thrive, growth retardation_x000D_
Tetany, osteomalacia, bone pain, hypocalcemia, infertility, dysmennorhea, amenorrhea_x000D_
Impaired absorption of fat soluble vitamins ADEK_x000D_ |
|
|
Term
| Malabsorption - Impaired Absorption of Fat Soluble Vitamins |
|
Definition
A - night blindness, hyperkeratosis, skin changes_x000D_
D - hypocalcemia, osteomalacia, rickets, hypophosphatemia_x000D_
E - neuropathy, hemolytic anemia_x000D_
K - prolongation of prothrombin time, easy brusing |
|
|
Term
| Malabsorption - Renal Manifestations |
|
Definition
Oxalate stone formation due to malabsorption of bile salts and fats_x000D_
Normally, most dietary oxalate precipitates in GI lumen as Calcium Oxalate and excreted in feces_x000D_
Saponifaction of luminal Calcium with excess fatty acids - soluble Sodium Oxalate salts form and are absobed_x000D_
Kidney excretes oxalate, forms calcium oxalate stones in ureter_x000D_
Fluid depletion due to diarrhea exacerbates stone formation |
|
|
Term
|
Definition
Most absorbed in duodenum - jejunum and ileum also contribute_x000D_
Clinical hypocalcemia presents as skeletal pain, tetany, paresthesia, osteoporosis, and stunted growth_x000D_
Absorption reduced if surface area is reduced or injured_x000D_
Fatty acid malabsorption saponifies luminal calcium and prevents absorption_x000D_
Vitamin D deficiency can impair absorption_x000D_
Must correct Ca measurement for hypoalbuminurea : add (4 - albumin g) x 0.8 to measured Ca |
|
|
Term
|
Definition
Benign smooth muscle derived tumor _x000D_
Most common in lower 1/3 of esophagus and in colon - may present with dysphagia_x000D_
Rare in stomach and small bowel _x000D_
Bland elongated spindle shaped cells, eosinophilic cytoplasm, expresses SM Actin and Desmin |
|
|
Term
| Gastrointestinal Stromal Tumor |
|
Definition
Mesenchymal tumor of GI tract - common in stomach and small intestine, rare in colon and esophagus_x000D_
Symptoms related to mass effect or anemia due to ulcerative blood loss_x000D_
Most driven by activating mutations in c-Kit or PDGFRa - activate tyrosine kinase signaling_x000D_
Derived from interstitial cells of Cajal - GI pacemaker cells in muscularis propria_x000D_
Prognosis based on size, mitotic index, and location - small intestine more aggressive than stomach_x000D_
Metastasize to serosal peritoneal nodules or liver - rarely spread outside abdomen_x000D_
Spindle cell (thin elongated cells), epithelioid type, or mixed histology_x000D_
Treat with surgical resection or imatinib tyrosine kinase inhibitor - exon 11 mutation responds well, exon 9 poorly_x000D_ |
|
|
Term
| Gastrointestinal Stromal Tumor - Synromes |
|
Definition
Neurofibromatosis Type 1_x000D_
Carney's triad - non hereditary syndrome affecting young females_x000D_
GIST, paragangilomas, pulmonary chomdroma |
|
|
Term
| Lymph Node - Zones and Cell Types |
|
Definition
Paracortex - T cells_x000D_
Mantle zone - naive B cells newly arrived from bone marrow --> Mantle Lymphoma_x000D_
Germinal Center - B cells interacting with dendritic cells --> Follicular Lymphoma_x000D_
Marginal zone - activated B cells --> MALToma |
|
|
Term
| Mucosa Associated Lymphoid Tissue Lymphoma (MALToma) |
|
Definition
Extra Nodal Marginal Zone B Cell Lymphoma_x000D_
Arise at sites of chronic inflammation - most commonly in GI Tract - stomach_x000D_
Most often arise in sites normally devoid of organized lymphoid tissue_x000D_
Indolent tumor can transform into aggressive diffuse large B cell lymphoma |
|
|
Term
|
Definition
Chronic inflammation (usually H pylori) drives formation of Gastric MALT_x000D_
MALT can progress to indolent extranodal marginal zone B cell lymphoma_x000D_
Lymphoepithelial lesions distinguish MALToma from chronic gastritis (lymphocytes don't invade epithelium)_x000D_
If associated with H pylori, infection drives NFkB signaling through MLT and BCL-10 signaling _x000D_
Translocations constituitively activating MLT and BCL-10 drive tumor progression_x000D_
Treat with antibiotics, remove inflammatory stimulus, reduce NFkB signaling --> tumor regression_x000D_
Tumors with t(11:18) AP12-MALT1 translocation do not respond to H pylori eradication --> transform into DLBCL_x000D_ |
|
|
Term
| GI Lymphomas - Important Genetic Alterations |
|
Definition
t(11:18) AP12-MALT1 - MALToma refractory to antibiotics --> transform into diffuse large B cell lymphoma_x000D_
t(11:14) IgH - Cyclin D1 - Mantle Cell Lymphoma - Naive Mantle Zone B Cell_x000D_
t(14:18) IgH-BCL2 - Follicular Lymphoma - Germinal Center B Cell_x000D_
t(8:14) IgH/k/l light chain - cMyc - Burkitt lymphoma - Mature B Cell_x000D_ |
|
|
Term
|
Definition
Clonal expansion of germinal center B cell - t(14:18) IgH - BLC2 prevents apoptosis_x000D_
Can be single mass like lesion or multiple lymphoid polyps (lymphomatous polyposis)_x000D_
Crowded follicles, monotonous clonal cell population, CD19+, CD20+, CD10+, Ig+, BCL6+, CD5-_x000D_
BCL2 + signature distinguishes follicular lymphoma from reactive follicular hyperplasia_x000D_
Indolent course with median survival 7 to 9 years - risk of transforming into aggressive DLBCL |
|
|
Term
| GI Lymphomatous Polyposis - Differential Diagnosis |
|
Definition
Reactive Lymphoid Hyperplasia_x000D_
Mantle Zone Lymphoma - most often presents in colon_x000D_
Follicular lymphoma - most often presents in small intestine |
|
|
Term
|
Definition
Clonal expansion of mantle zone (naive) B cells - t(11:14) IgH - Cyclin D1 drives G1 to S progression_x000D_
Most often presents in colon with lymphomatous polyposis_x000D_
Nodular lymphoid aggregates, monomorphic cells, condensed chromatin, scant cytoplasm, inconspicuous nucleoli_x000D_
Aggressive, median survival < 5 years_x000D_ |
|
|
Term
| GI Diffuse Large B Cell Lymphoma |
|
Definition
| High grade aggressive neoplastic mature B cell lesion_x000D_ Express B cell markers CD19 and CD20_x000D_ Present as rapidly enlarging mass at nodal or extranodal site - rapidly fatal_x000D_ Activating mutations of BCL6 - represses germinal center B cell differentiation and arrest_x000D_ |
|
|
Term
|
Definition
High grade aggressive neoplastic mature B cell - derived from germinal center B cell_x000D_
t(8:14) Igh - cMyc translocation or t(2:8) k light chain - cMyc or t(8:22) l light chain - cMyc_x000D_
Endemic - presents as mandible mass, 100% infected with EBV_x000D_
Sporadic - ileocecum and peritoneum involvement, 15% infected with EBV_x000D_
Immunodeficient associated - abdominal involvement, 25% infected with EBV_x000D_
Abdominal involvement may cause pain, nausea, vomiting, obstruction, GI bleeding_x000D_
High mitosis, high apoptosis, debris phagocytosed by macrophages creates clear cytoplasm --> starry sky |
|
|
Term
| Enteropathy Type T Cell Lymphoma |
|
Definition
Aggressive lymphoma of intraepithelial T lymphocytes _x000D_
High association with Celiac disease - especially if not responding to gluten free diet_x000D_
Intraepithelial T cells acquire cellular atypia, aberrant T cell antigen expression and clonal gene rearrangement_x000D_
Most often involves jejunum or ileum_x000D_
Neoplastic lymphocytes within background of mixed inflammatory cells recruited by T cell cytokine release |
|
|
Term
| Enteric Nervous System - Actions of Neurotransmitters |
|
Definition
Intestinal enterochromaffin cells release 5 HT in response to pressure and other stimuli_x000D_
Binding to 5 HT3 R on extrinsic afferent nerves induces nausea, vomiting, and abdominal pain_x000D_
Binding to 5 HT1P R on intrinsic primary afferent nerves (IPAN) stimulate motility and regulates peristalsis_x000D_
Binding to 5 HT4 R on presynaptic IPAN terminals enhances release of ACh and CGRP onto interneurons_x000D_
Extrinsic input mediated by ACh - binding to M3 receptors stimulates motility_x000D_
Extrinsic DA reduces cholinergic effects via D2 receptors _x000D_ |
|
|
Term
|
Definition
Vomiting center located in medullary reticular formation next to Chemoreceptor Trigger Zone (area postrema)_x000D_
CTZ located at base of 4th ventricle - no BBB allows monitoring of blood and CSF composition_x000D_
CTZ enriched for receptors - Histamine, 5 HT3, D2, NK1, Mu opioid_x000D_
Neural input to vomiting center from CTZ, vestibular apparatus, vagus and splanchnic afferents, and cerebral cortex_x000D_ |
|
|
Term
|
Definition
H1 receptors in emesis circuitry stimulate nausea and vomiting_x000D_
Reversible H1 antagonists act as antiemetics_x000D_
H1 antagonists with antimuscarinic effects used for motion sickness and vertigo |
|
|
Term
|
Definition
5 HT3 receptors in GT tract and vomiting center precipitate vomiting reflex_x000D_
Especially important for vomiting triggered by chemicals _x000D_
Chemotherapy drugs induce increased 5 HT release from EC cells to stimulate afferent vagals to CTZ_x000D_
5 HT3 Antagonists effective for n/v associated with chemotherapy or post operative pain_x000D_
Central and peripheral antagonism - no cross reactivity with D2 receptors --> no extrapyramidal side effects_x000D_
Side effect of constipation may be used to treat diarrhea |
|
|
Term
|
Definition
Inhibitory modulatory effect - inhibits ACh input to smooth muscle to decrease esophageal and gastric motility_x000D_
Antiemetic D2 antagonists also have activity at histamine, ACh and 5 HT3 receptors_x000D_
Used in chemotherapy sickness, motion sickness_x000D_
Metoclopramide is prokinetic used to treat diabetic gastroparesis_x000D_
Extrapyramidal side effects due to D2 activity |
|
|
Term
|
Definition
M1 receptor colocalizes with Histamine R in cerrebellum_x000D_
M1 antagonists (scopolamine) administered as transdermal patch for motion sickness |
|
|
Term
|
Definition
NK1 receptor antagonists exert antiemetic effect through central blockade in CTZ_x000D_
Aprepitant - highly selective NK1 Receptor antagonist_x000D_
Used for chronic nausea in chemotherapy patients |
|
|
Term
|
Definition
| CB1 receptors near CTZ inhibit emesis and stimulate appetite |
|
|
Term
| GI Motility - Metoclopramide |
|
Definition
D2 receptor antagonist - increases ACh release from myenteric neurons - stimulates motility_x000D_
Indicated for diabetic gastroparesis, antiemetic agent, 3rd line therapy for GERD_x000D_
Extrapyramidal side effects limits use - restlessness, tremor, drowsiness |
|
|
Term
| GI Motility - Bethanechol |
|
Definition
Cholinergic M3 receptor agonists_x000D_
Stimulates gastric emptying_x000D_
Indicated for autonomic neuropathy - gastroparesis_x000D_
Absorbed systemically - can also treat GERD and urinary retention due to autononomic neuroapthy_x000D_ |
|
|
Term
|
Definition
Binding to motilin receptors stimulates gastric motility_x000D_
Endogenous motilin released from pancreas and intestinal EC cells_x000D_
Erythromycin can act as motilin receptor agonist_x000D_
Indicated in for diabetic gastroparesis |
|
|
Term
| Achalasia Hypermotility Syndrome - Medical Therapy |
|
Definition
Anticholinergics - decrease motility_x000D_
Calcium channel antagonists - inhibit smooth muscle contraction and spasms_x000D_
Botulinum toxin type A - inhibits ACh release from vesicles |
|
|
Term
| Constipation - Stimulant Laxatives |
|
Definition
Increase intestinal motility _x000D_
Increase small intestine fluid secretion and decrease colonic reabsorption_x000D_
Not good for chronic use_x000D_
Caffeine, nicotine, fats, calories |
|
|
Term
| Constipation - Bulk Forming Laxatives |
|
Definition
Complex polysaccharides or cellulose derivatives - fiber_x000D_
No systemic absorption_x000D_
Ingest with lots of water to prevent obstruction_x000D_
May also help lower LDL |
|
|
Term
| Constipation - Osmotic Laxatives |
|
Definition
Hyperosmolar agents - induce movement of water into lumen_x000D_
Magnesium oxide, sorbitol, lactulose, magnesium citrate_x000D_
Polyethylene glycol used as bowel prep |
|
|
Term
| Constipation - Lubricant Laxatives |
|
Definition
Mineral oils that coat bowel - reduce water absorption in colon_x000D_
Used for chronic constipation refractory to bulking agents_x000D_
Causes malabsorption of fat soluble vitamins and perianal irritiation |
|
|
Term
| Constipation - Stool Softners / Emollient Laxatives |
|
Definition
Increase water secretion from small intestine and colon_x000D_
Act as surfactant to increase fecal mixing_x000D_
Used to treat post operative constipation in inpatients |
|
|
Term
|
Definition
5 HT4 receptor agonists_x000D_
Increases ACh release in myenteric neurons in stimulate GI motility_x000D_
Tegaserod Maleate - withdrawn due to risk of MI mediated by K channel effects_x000D_
Prucalopride has better SE profile_x000D_ |
|
|
Term
| Constipation - Chloride Channels |
|
Definition
Lubiprostone stimulates type 2 Cl channels in small intestine_x000D_
Increase water secretion into lumen_x000D_
Nausea limits dosing and use |
|
|
Term
|
Definition
Synthetic somatostatin analogue_x000D_
Inhibits 5 HT release --> reduces GI motility_x000D_
Used for idiopathic secretory diarrhea and diarrhea caused by neuroendocrine tumors (VIP, gastrin, 5 HT)_x000D_
SE of hyperglycemia (inhibits insulin) and delayed gall bladder emptying and gall stone formation |
|
|
Term
| Diarrhea - Bismuth Subsalicylate |
|
Definition
Inhibits small bowel secretions - bacteriocidal activity --> antiflatulence_x000D_
Decreases stool frequency and abdominal pain_x000D_
SE of encephalopathy, renal toxicity, black stools, and rare salicylate toxicity |
|
|
Term
|
Definition
Muscarinic receptor antagonists slow GI motility_x000D_
SE of tachycardia, dry mouth, fatigue, respiratory depression |
|
|
Term
|
Definition
Opioid agonists_x000D_
Decrease peristalsis in small intestine, increase internal anal sphincter tone_x000D_
Decreases fluid and electrolyte secretion_x000D_
Reduces stool volume and abdominal cramps_x000D_
SE of CNS and respiratory depression, delayed gastric emptying, addictive potential |
|
|
Term
|
Definition
5 HT3 receptor antagonists - Alosetron_x000D_
Decrease gut afferent signaling - reduces symptoms of nausea, bloating, and abdominal pain_x000D_
Indicated for short term IBS treatment _x000D_
SE of severe constipation and ischemic colitis |
|
|
Term
| Liver - Anatomic and Functional Lobes |
|
Definition
Anatomic border - falciform ligament - separates smaller left lobe from larger right, caudate, and quadrate lobe_x000D_
Functional border lies on vertical plane from IVC to gallbladder - separate bile drainage_x000D_
Left functional lobe includes caudate and quadrate lobe_x000D_
Liver can be divided into 8 resectable segments with independent blood supply and biliary drainage |
|
|
Term
| Pancreas - Collateral Circulation in Head of Pancreas |
|
Definition
Celiac --> Gastroduodenal --> Anterior and Posterior SUPERIOR Pancreatoduodenal Arteries_x000D_
SMA --> Anterior and Posterior INFERIOR Pancreatoduodenal Arteries_x000D_
Anastamoses in head of pancreas provides route for collateral circulation |
|
|
Term
|
Definition
Inferior Mesenteric Vein drains into Splenic Vein_x000D_
Superior Mesenteric Vein joins with Splenic Vein to form Portal Vein posterior to neck of pancreas_x000D_
Left gastric vein (lesser curvature of stomach and abdominal esophagus) drains directly into Portal Vein |
|
|
Term
| Sites of Porta-Caval Anastomoses |
|
Definition
Umbilicus - Paraumbilical Veins --> Superficial Abdominal Wall Veins ==> Caput Medusa_x000D_
Rectum - Sup Rectal Veins --> Mid/Inf Rectal Veins ==> Internal Hemorrhoids_x000D_
Esophagus - Gastric Veins --> Azygous Esophageal Veins ==> Esophageal Varicies |
|
|
Term
|
Definition
Located in mouth and esophagus_x000D_
Secrete digestive enzymes (amylase), lipids and proteins that strengthen tooth enamel_x000D_
Secrete lysozymes to prevent bacterial growth and IgA_x000D_
Serous glands - neutral pH_x000D_
Mucin glands - acidic pH, basophillic staining |
|
|
Term
| Pancreas - Acinar and Ductal Cells |
|
Definition
Derived from same stem cell population_x000D_
Stem cells located at transition zone of acini and duct_x000D_
Duct - glandular cells secrete mucin and bicarbonate_x000D_
Acini - pyramidal cell, secrete bicarbonate and digestive enzymes_x000D_ |
|
|
Term
| Liver - Blood Supply to Hepatocytes |
|
Definition
Portal vein provides 60-70% of nutrient rich deoxygenated blood from abdominal GI tract_x000D_
Hepatic artery provides 30-40% of oxygenated blood _x000D_
Enter liver through hilum / porta hepatis_x000D_
Branches travel in parallel portal tracts with bile duct branches carrying bile in reverse direction_x000D_
Blood from both sources mix in sinusoids |
|
|
Term
|
Definition
Branches of Portal Vein, Hepatic Artery, and Bile Duct_x000D_
Portal vein is largest_x000D_
Hepatic Artery and Bile Duct are the same size - HA has thick muscular wall_x000D_
Form peripheral points of hepatic lobules _x000D_ |
|
|
Term
|
Definition
Space between hepatocytes and endeothelium lining the sinusoids_x000D_
Hepatocyte microvilli protrude into space_x000D_
Hepatic stellate cells reside in space of Disse - store fat soluble vitamins (A)_x000D_
Sinusoidal lumen blood --> endothelial cell --> space of Disse --> Hepatocyte_x000D_ |
|
|
Term
| Liver- Ito / Stellate Cells |
|
Definition
Mesenchymal cells that reside in space of Disse_x000D_
Storage of fat and fat soluble vitamins - hypertrophic in hypervitaminosis A_x000D_
TGFb stimulates them to secrete Type I collagen _x000D_
Contribute to liver scarring and cirrhosis - TGFb released by hepatocytes and kuppfer cells |
|
|
Term
|
Definition
Type I - surrounds portal vein and central vein - stains blue with Trichrome stain_x000D_
Type III - lines space of Disse in hepatic cords, visualized with reticulin stain_x000D_ |
|
|
Term
| Liver - Acinus Zone Model |
|
Definition
Pyramid formed by two portal tracts at the base and central vein at the apex_x000D_
Zone 1 is closest to portal veins - oxygen and nutrient supply - glycogen and plasma protein synthesis_x000D_
Zone 2 is intermediate_x000D_
Zone 3 is furthest from afferent blood - enriched for p450 enzymes_x000D_
Zone 3 most sensitive to oxidative damage and ischemic damage_x000D_ |
|
|
Term
| Liver - Hepatocyte Zone Metabolic Functions |
|
Definition
Zone 1 - glycogen synthesis and plasma protein synthesis_x000D_
Zone 3 - lipid, drug, and alcohol metabolism and detoxification, enriched for p450 |
|
|
Term
| Gall Bladder - Structure of Wall |
|
Definition
Lined by epithelium, lamina propria, and muscularis propria_x000D_
No submucosa or muscularis propria layers |
|
|
Term
|
Definition
Embryologic malformation in which dorsal pancreatic duct does not fuse with ventral duct_x000D_
Secretions from dorsal duct directly enter duodenum via a minor duct (Santorini)_x000D_
Dorsal duct empties proximal to Ampulla of Vater_x000D_
Not clinically significant |
|
|
Term
| Pancreatic Insuloacinar Portal System |
|
Definition
Venous blood from islets perfuses nearby acini before entering portal vein_x000D_
Islet hormones can exert local effect on exocrine function_x000D_
Insulin stimulates exocrine function - glucagon and somatostatin inhibit exocrine function |
|
|
Term
|
Definition
Released into systemic circulation by intestinal cells detecting acid in lumen - pH < 4.5_x000D_
Secretin binding to pancreatic exocrine duct acinar cells activates adenylate cyclase and CFTR_x000D_
Opens apical Cl channel --> Cl efflux --> Bicarbonate exchanged for Cl --> Bicarbonate secretion_x000D_
Reduces gastric emptying and promotes mesenteric blood flow |
|
|
Term
| Pancreatic Enzyme Secretions |
|
Definition
Amylase and Lipase - synthesized and secreted in active forms_x000D_
Other enzymes secreted as inactive proenzymes_x000D_
Brush border enterokinase converts trypsinogen to trypsin_x000D_
Trypsin activates other enzymes_x000D_
Trypsinogen, Chymotrypsinogen, Proelastase, Procarboxypeptidase_x000D_
Alpha amylase, Lipase, Procolipase, Prophospholipase A2, Carboxylesterase lipase_x000D_
DNAse, RNAse |
|
|
Term
| Pancreas - Mechanisms to Prevent Autodigestion |
|
Definition
Proteolytic enzymes stored as inactive zymogens _x000D_
Peptide inhibitor of trypsin (PSTI or SPINK1) in cytosol inactivate any active trypsin_x000D_
Protease inhibitors (alpha 1 antitrypsin and alpha 2 microglobulin) in pancreatic interstitium and blood |
|
|
Term
|
Definition
Pancreatic and salivary isoforms - salivary initiates starch digestion_x000D_
Functions at neutral pH - requires bicarbonate secretion to neutralize gastric acid_x000D_
Splits 1,4 glycoside linkages - cannot split 1,6 glycoside linkages_x000D_
Generates maltose, maltotriose, and limit dextrans containing 1,6 linkages_x000D_
Brush border enzymes continue digestion to glucose |
|
|
Term
|
Definition
Pancreatic lipase functions at neutral pH - requires bicarbonate secretion to neutralize gastric acid_x000D_
Binds to oil/water interface of triglyceride droplets - hydrolyzes TG into 2 FA and MG_x000D_
Bile salts coat outside of lipid droplet - co lipase increases activity of lipase |
|
|
Term
| Pancreas - Proteolytic Enzymes |
|
Definition
Secreted as inactive zymogen proenzymes_x000D_
Brush border enterokinase activates trypsinogen into trypsin_x000D_
Trypsin activates other proenzymes_x000D_
Includes trypsin, chymotrypsin, and elastase |
|
|
Term
| Pancreas - Regulation of Enzyme Secretion |
|
Definition
Increases in cAMP and Calcium in cytoplasm increase vesicle fusion and enzyme secretion_x000D_
VIP and Secretin --> cAMP --> PKA --> Secretion_x000D_
CCK, ACh, GRP, Substance P --> PLC --> Ca --> Secretion_x000D_
Synergistic effects when both signals received |
|
|
Term
| Pancreas - Cholecystokinin (CCK) |
|
Definition
Produced by proximal intestinal cells in response to peptides, amino acids, and fatty acids in lumen_x000D_
Stimulates exocrine pancreatic secretion and insulin secretion_x000D_
Contracts gallbladder, releases sphincter of Oddi, delays gastric emptying_x000D_
Elevated serum levels after meal ingestion |
|
|
Term
| Pancreas - Cephalic Phase of Secretion |
|
Definition
Mediated by vagus nerve_x000D_
Chewing food without swallowing elicits 50% of maximal pancreatic enzyme secretion_x000D_
Blocked by Atropine - mACH |
|
|
Term
| Pancreas - Gastric Phase of Secetion |
|
Definition
Vagovagal reflex arc_x000D_
Stimulated by gastric distension |
|
|
Term
| Pancreas - Intestinal Phase of Secretion |
|
Definition
Stimulated by acid and chyme in intestinal lumen_x000D_
Hormonal - CCK, Secretin released from mucosa at pH < 4.5 _x000D_
Neural - enteropancreaic vagovagal reflex stimualtes secretion_x000D_
Products of digestion - peptides, amino acids, fatty acids - stimulate enzyme secretion_x000D_ |
|
|
Term
| Pancreas - Post Prandial Inhibition of Secretion |
|
Definition
Intraluminal trypsin not complexed to protein inhibits CCK release_x000D_
Oleic acid in distal ileum inhibits gastric emptying and pancreatic secretion - mediated by peptide YY_x000D_
Intravenous amino acids and glucose inhibit CCK release via glucagon and somatostatin |
|
|
Term
| Pancreas - Test of Function |
|
Definition
93% of ingested fat should be absorbed - < 7% should be present in stool_x000D_
Maldigestion results in excess fat and protein in stool - excess carbs digested by colonic bacteria_x000D_
Steatorrhea develops when enzyme function falls to <10% of normal --> pancreatic insufficiency_x000D_
Detect milder disease by measuring duodenal secretion post prandial or with structural tests |
|
|
Term
|
Definition
Absorption of fat and fat soluble vitamins_x000D_
Excretion of polar metabolites from water insoluble waste products - bilirubin_x000D_
Excretion of cholesterol - directly and as bile derived from cholesterol |
|
|
Term
| Bile - Bile Salts Affecting Canalicular Flow |
|
Definition
Ursodeoxycholate increases canicular flow_x000D_
Lithocholate reduces flow - cholestasis |
|
|
Term
| Bile - Secretion into Canaliculus |
|
Definition
Bilirubin and bile salts are transported, metabolized, and secreted through seperate pathways_x000D_
Secreted from hepatocyte into canaliculus against concentration gradient - ATP dependent rate limiting step_x000D_
Farnesoid X factor nuclear receptor detects intracellular bile _x000D_
FXR increases canalicular secretion and suppresses bile salt synthesis_x000D_
Prevents accumulation of toxic intracellular bile_x000D_ |
|
|
Term
| Bile - Bile Salt Synthesis |
|
Definition
Acetate --(HMG CoA Reductase)--> cholesterol_x000D_
7a hydroxylation (rate limiting) and and Carboxylation of cholesterol _x000D_
7a hydroxylase stimulated by depletion of bile salt pool_x000D_
7b hydroxylation to ursodeoxycholic acid increases water solubility _x000D_
Primary bile salts synthesized by hepatocytes - cholic and chenodeoxycholic_x000D_
Secondary bile salts made by bacteria removing or isomerizing 7 OH - deoxycholic, urso, and lithocholic |
|
|
Term
| Bile - Bile Salt Conjugation |
|
Definition
Before secretion, carboxyl side chains are conjugated with taurine or glycine_x000D_
Conjugation lowers pK, increases ionization of bile salts_x000D_
Ionization prevents back diffusion in bile duct and small intestine and limits intestinal absorption_x000D_
Conjugation allows binding and reabsoption by receptors in ileum |
|
|
Term
|
Definition
Critical Micellar Concentration (CMC) - above which bile salts will form micelles_x000D_
Hyrdophillic portions external, hydrophobic portions internal_x000D_
Solubilization of lipids - cholesterol, phosphilipids - and fat soluble vitamins occurs in interior_x000D_
Addition of lecithin phospholipid creates mixed micelle - increased ability to solubilize cholesterol and lipids |
|
|
Term
| Bile - Enterohepatic Circulation |
|
Definition
95% of conjugated bile salts absorbed bile ileum receptors and returned to liver via portal vein_x000D_
Liver synthesis equals fecal loss_x000D_
Increased fecal loss with ileal disease or resection |
|
|
Term
| Bile - Bacterial Alteration |
|
Definition
Deconjugation of amino acids from bile salts - reduces ionization_x000D_
7 OH removal or isomerization to produce secondary bile salts_x000D_
Deionized salts can precipitate in slightly acidic environment of small intestine _x000D_
Bacterial overgrowth --> increased deconjugation and deionization --> precipitation_x000D_
Can result in inadequate micelle formation and lipid and vitamin malabsorption_x000D_ |
|
|
Term
| Bile - Specific Bile Salts |
|
Definition
Primary bile salts most abundant - cholic and chenodeoxycholic_x000D_
Deoxycholic is major secondary bile salt_x000D_
Lithocholic acid is toxic - can cause cholestasis _x000D_
Liver adds sulfate radical to lithocholic acid resulting in excretion in stool or urine |
|
|
Term
| Bile - Cholesterol Secretion |
|
Definition
Cholesterol and Phospholipids secreted into canaliculi as bilayered water soluble vesicles_x000D_
Vesicles fuse with bile salt micelles to produce mixed micelles in bile ducts and gallbladder_x000D_
Cholesterol and phospholipids protect hepatocytes, bile duct and gallbladder mucosa from bile salt damage |
|
|
Term
|
Definition
Serous salivary glands - paired at angle of mandible_x000D_
Drain inside the cheek through Stensen's duct_x000D_
25% of saliva volume |
|
|
Term
|
Definition
Mixed serous / mucous glands paired inside the lower edge of mandible_x000D_
Predominance of serous cells_x000D_
Drain in the floor of the mouth near base of tongue through Wharton's duct_x000D_
70% of saliva |
|
|
Term
|
Definition
Mixed serous / mucous glands paired at base of tongue_x000D_
Predominance of mucous cells_x000D_
Drain into mouth through multiple small ducts_x000D_
5% of saliva |
|
|
Term
|
Definition
CSF - dark, low signal_x000D_
Fat - white, high signal_x000D_
Liver - intermediate / high signal_x000D_
Spleen - intermediate / low signal_x000D_
Metastatic liver disease has similar intensity as spleen_x000D_
Cysts and hemanagiomas look like CSF |
|
|
Term
|
Definition
CSF - bright, high signal_x000D_
Fat - dark, low signal_x000D_
Liver - intermediate / low signal_x000D_
Spleen - intermediate / high signal_x000D_
Metastatic liver disease has similar intensity as spleen_x000D_
Cysts and hemanagiomas look like CSF |
|
|
Term
| Hepatobiliary Bile Duct Drainage |
|
Definition
Right and Left Hepatic ducts fuse to form common hepatic duct_x000D_
Cystic duct joins with common hepatic duct to form common bile duct_x000D_
Common bile duct joins with main pancreatic duct to form Ampulla of Vater |
|
|
Term
| Endoscopic Retrograde Cholangio Pancreatography (ERCP) |
|
Definition
Endoscopic tube into duodenum to ampulla of vater_x000D_
Send out smaller camera to ascend up common bile duct or pancreatic duct |
|
|
Term
| GI Imaging - Double Duct Sign |
|
Definition
Appearance of dilated common bile duct and pancreatic duct - lack of fusion_x000D_
Indicates obstruction - usually pancreatic cancer |
|
|
Term
| Acute Pancreatitis - Definition |
|
Definition
Reversible pancreatic parenchymal injury associated with inflammation_x000D_
Clinically defined as having 2/3 :_x000D_
Typical pain - mid epigastric, acute onset, non undulating, referred to upper back and left shoulder_x000D_
Radiographic findings_x000D_
Elevations in blood chemistires (amylase or lipase) - long latency between onset and elevation |
|
|
Term
| Acute Pancreatitis - Pathogenesis |
|
Definition
Inappropriate activation of trypsin --> activates other proenzymes --> autodigestion_x000D_
Local fat digestion by lipase - synthesized in active form_x000D_
Trypsin activates prekalikrein --> Factor XII --> activation of clotting and complement systems_x000D_
Inflammation and small vessel thromboses --> congestion and rupture of blood vessels_x000D_
Cytokine release by injured tissue, periacinar myofibroblasts, and leukocytes --> interstitial edema |
|
|
Term
| Acute Pancreatitis - Destructive and Protective Factors |
|
Definition
Damaging - bile, low pH, trypsin, cathepsin B, high Ca, CCK, triglycerides_x000D_
Protective - SPINK1, mesotrypsin, alpha 1 antitrypsin, enzyme Y, alpha 2 microglobulin, somatostatin |
|
|
Term
| Acute Pancreatitis - Propagation of Inflammation and Damage |
|
Definition
Trypsin activates prekalikrein --> Factor XII --> activation of clotting and complement systems_x000D_
TNF, IL 1, IL 6, and Platelet Activating Factor, complement activation, oxygen free radicals --> leaky vessels_x000D_
Edema, vascular insufficiency and ischemic injury_x000D_
Phospholipase A2 --> destruction of surfactant --> Acute Respiratory Distress Syndrome_x000D_
Thrombin activation --> Splenic Vein Thrombosis and / or DIC_x000D_ |
|
|
Term
| Acute Pancreatitis - Etiologies |
|
Definition
Biliary tract disease and alcoholism - 80%_x000D_
Gallstones, triglycerides, tumor obstruction, ischemia, hypercalcemia, scorpions_x000D_
Infection - mumps_x000D_
Drugs - byetta_x000D_
Hereditary - deficiency in trypsin inactivation |
|
|
Term
| Acute Pancreatitis - Biliary Etiology |
|
Definition
Most common cause - gallstones or biliary sludge - obstruction in ampulla of Vater_x000D_
Increased intrapancreatic ductal pressure - accumulation of enzyme secretions in interstitium_x000D_
Lipase secreted in active form - local fat necrosis --> release of inflammatory cytokines_x000D_
Inflammation, leaky vasculature, interstitial edema --> ischemic injury_x000D_
Can result in necrotizing pancreatitis _x000D_
ALT will be 3x upper limit of normal (>150)_x000D_ |
|
|
Term
| Acute Pancreatitis - Alcohol Etiology |
|
Definition
Chronic alcohol ingestion increases protein rich pancreatic fluid - obstruction by protein plug_x000D_
If patient stops chronic drinking, increases fat and protein ingestion --> increased CCK_x000D_
Direct toxic effects on acinar cells - mitochondiral toxin, lysosomal instability_x000D_
Generates ROS, inflammation |
|
|
Term
| Acute Pancreatitis - Triglyceride Etiology |
|
Definition
Occurs with TG > 500, endocrine emergency if > 1000_x000D_
Alcohol ingestion or uncontrolled hyperglycemia can increase triglycerides_x000D_
Amylase and Lipase may appear normal - elevated TG interfere with assay |
|
|
Term
| Acute Pancreatitis - Trauma |
|
Definition
Disruption of pancreatic duct where it crosses the spine_x000D_
After acute care, need ERCP to connect duct with stent to prevent tail apoptosis |
|
|
Term
| Acute Pancreatitis - Drug Induced Etiology_x000D_ |
|
Definition
Early - hypersensitivity or direct damage - Azathiaprine, 6MP, sulfa, flagyl, ACE I, salicyclates_x000D_
Late - IgG or T cell related, build up of toxic metabolites - Didanosine, pentamidine, valproic acid_x000D_
Hypertriglyceridemia - tamoxifen, estrogen, finasteride, beta blockers, vit A, thiazides_x000D_
Angioedema - ACE inhibitors_x000D_
Directly Toxic - sulfa, diuretics |
|
|
Term
| Acute Pancreatitis - Clinical Presentation |
|
Definition
Acute onset abdominal pain_x000D_
Constant, non undulating, intense - referred to upper back or left shoulder_x000D_
Nausea, vomiting, syncope, tachycardia, fevers, oliguria, tachypnea, hypotension_x000D_
Elevated plasma amylase (24 hrs) and lipase (72-96 hrs)_x000D_
Cullen's and Grey Turner signs - poor prognosis_x000D_
Subcutaneous Fat Necrosis |
|
|
Term
|
Definition
Brusing of flanks during acute pancreatitis_x000D_
Indicates intrabdominal bleeding - predicts severe disease course and high mortality |
|
|
Term
|
Definition
Superficial bruising and edema of sub cutaneous fat around umbilicus_x000D_
Predicts severe disease course and high mortality in acute pancreatitis |
|
|
Term
| Acute Pancreatitis - Mortality |
|
Definition
Early - multisystem organ failure, DIC, hypocalcemia, shock, hypotension, compartment syndrome_x000D_
Aspiration, cholangitis, acidosis, hemorrhagic pancreatitis, intestinal ischemia from clotting_x000D_
Late - pancreatic abscess, infectious necrosis, secondary biliary obstruction, hypoalbuminemia, PE |
|
|
Term
| Acute Pancreatitis - Imaging |
|
Definition
CT to rule our alternative diagnosis, to detect necrosis or abscess_x000D_
Dont use CT contrast - renal dysfunction occurs early_x000D_
US - check for obstructive gall stones |
|
|
Term
| Acute Pancreatitis - Therapy |
|
Definition
Supportive IV fluids and analgesia_x000D_
Restrict oral intake or TPN to limit pancreatic activity_x000D_
Hydration_x000D_
Antibiotics is cholangitis is suspected or infectious necrosis_x000D_
Surgery if patient is unstable, infected necrosis, abdominal compartment syndrome, or gall stone obstruction |
|
|
Term
| Acute Pancreatitis - Morphology |
|
Definition
Microvascular leakage causing edema_x000D_
Necrosis of Fat by lipases_x000D_
Acute inflammation_x000D_
Proteolytic destruction of parenchyma_x000D_
Interstitial hemorrhage_x000D_
Spots of hemorrhage interspersed with yellow chalky fat necrosis |
|
|
Term
| Acute Pancreatitis - Severity Predictors |
|
Definition
HR > 60, Age > 44, BMI > 25/30_x000D_
WBC > 16, Glucose > 200, LDH > 350, AST >250_x000D_
pO2 < 60 mmHg, Systolic BP < 90, Creatinin > 2, GI bleeding_x000D_
DIC - platelets <100, fibrinogen < 1, D dimers > 80 |
|
|
Term
| Chronic Pancreatitis - Definition |
|
Definition
| Irreversible destruction of exocrine parenchyma, fibrosis, and eventual destruction of endocrine parenchyma |
|
|
Term
| Chronic Pancreatitis - Pathogenesis |
|
Definition
Repeated episodes of acute pancreatitis initiates perilobular fibrosis, duct distortion, and altered secretions_x000D_
Ductal obstruction by protein plugs from increased protein content of secretions - plugs may calcify_x000D_
Toxins - EtOH - direct toxic effects on acinar cells_x000D_
Oxidative Stress - EtOH induced, free radical damage, activation of AP1 and NFkB_x000D_
Profibrogenic chemokines |
|
|
Term
| Chronic Pancreatitis - Morphology and Histology |
|
Definition
Parenchymal fibrosis, reduced number and size of acini, relative sparing of islets_x000D_
Variable dilation of pancreatic ducts_x000D_
Chronic inflammatory infiltrate |
|
|
Term
| Chronic Pancreatitis - Clinical Features |
|
Definition
Variable presentation - repeated attacks of pain, jaundice, indigestion_x000D_
May be silent until full pancreatic insufficiency and diabetes mellitus develop_x000D_
May be precipitated by EtOH abuse, overeating, use of opiates_x000D_
Results in chronic pain, steatorrhea, diabetes, biliary obstruction, B12 deficiency, cancer |
|
|
Term
|
Definition
Fusion of pancreatic duct with common bile duct_x000D_
True structural sphincter - controls flow of bile and pancreatic secretions into duodenum_x000D_
Lumen is lined by ductal epithelium - surface is lined by duodenal mucosa_x000D_
Surgical resection of head of pancreas requires excising part of the duodenum |
|
|
Term
| Pancreatobiliary Maljunction |
|
Definition
Fusion of pancreatic duct and common bile duct proximal to ampulla of vater_x000D_
Smalle area creates increased pressure_x000D_
Pancreatic duct pressure is greater than common bile duct pressure_x000D_
Reflux of pancreatic secretions into biliary tree |
|
|
Term
|
Definition
Localized collection of necrotic-hemorrhagic material rich in pancreatic enzymes_x000D_
Form by walling off of peripancreatic hemorrhagic fat necrosis with fibrous tissue_x000D_
Non epithelial lined fibrous walls of granulation tissue_x000D_
Commonly arise after acute pancreatitis, chronic alcoholic pancreatitis, or traumatic injury_x000D_
Usually resolve but can become infected or grow large enough to compress or perforate into adjacent structures |
|
|
Term
| Cystic Fibrosis of the Pancreas |
|
Definition
CFTR Mutation --> abnormal chloride secretion --> viscous pancreatic secretions_x000D_
May develop exocrine pancreatic insufficiency due to atrophy of acini_x000D_
Atrophy due to prolonged plugging of small ducts with viscous mucous - not inflammation_x000D_
Typically do not develop fibrosis associated with chronic pancreatitis |
|
|
Term
| Autoimmune Pancreatitis / Lymphoplasmacytic Sclerosing Pancreatitis |
|
Definition
Chronic pancreatitis mediated by autoimmune attack_x000D_
Characterized by duct centric mixed inflammatory infiltrate, venulitis, and hypergamma globulinemia_x000D_
Diffuse enlargement of pancreas, narrowing of main duct_x000D_
Stenosis of pancreatic portion of common bile duct --> cholestatic liver dysfunction_x000D_
Responds to steroids_x000D_
May clinically mimic pancreatic cancer - presents with pain, jaundice, +/- mass |
|
|
Term
| Pancreatic Ductal Adenocarcinoma - Overview |
|
Definition
Most common pancreatic malignancy - highly aggressive_x000D_
Most occur in pancreatic head - obstruct bile duct and present as painless jaundice_x000D_
Mutations in KRAS (oncogene) and p16 (tumor suppressor) result in dysplasia progression to carcinoma_x000D_
Elicit desmoplastic stromal response of fibroblasts, lymphocytes, and ECM _x000D_
Commonly present at advanced stage - local invasion and distant metastasis _x000D_ |
|
|
Term
| Pancreatic Ductal Adenocarcinoma - Clinical Features |
|
Definition
Remain silent until invade and compromise adjacent structures_x000D_
Obstructive jaundice, weight, loss, anorexia, malaise and weakness_x000D_
Migratory thrombophlebitis - Trousseau sign - releasing of coagluation factors by tumor_x000D_
Can directly invade spleen, adrenals, vertebrae, transverse colon, stomach - perineural invastion_x000D_
Spread to peripancreatic, gastric, mesenteric, omental, and portahepatic lymph nodes_x000D_
Distant metastasis to liver, lungs, and bones |
|
|
Term
| Pancreatic Ductal Adenocarcinoma - Inherited Syndromes |
|
Definition
Familial atypical mole malignant melanoma - p16 mutation_x000D_
Peutz Jegher's _x000D_
HNPCC_x000D_
Hereditary pancreatitis_x000D_
BRCA2 |
|
|
Term
| Pancreatic Endocrine Tumors |
|
Definition
May be non functioning, insulinomas, gastrinomas, VIPomas, or glucagonoma_x000D_
Most insulinomas are benign - most other tumors are aggressive and malignant_x000D_
Slightly higher mortality with non functional tumors_x000D_
Presence of necrosis and high mitotic index are important prognostic factors _x000D_
Requires metastasis or invasion of adjacent organ to be diagnosed as pancreatic endocrine carcinoma |
|
|
Term
| Pancreatic Congenital Cysts |
|
Definition
Anamolous development of pancreatic ducts_x000D_
Usually single, thin walled, lined by epithelium, enclosed by thing fibrous capsule, clear serous fluid_x000D_
May be part of autosomal dominant polycystic kidney disease of VHL disease_x000D_
Majority are benign - may become infected or perforate into adjacent structures_x000D_
10% are neoplastic |
|
|
Term
| Pancreatic Serous Cystadenoma |
|
Definition
Benign cystic neoplasm _x000D_
Lined by glycogen rich cuboidal cells, clear straw colored fluid_x000D_
May present with non specific abdominal pain or palpable abdominal mass_x000D_
Almost always benign |
|
|
Term
| Pancreatic Mucinous Cystic Neoplasm |
|
Definition
Cystic mass associated with invasive carcinoma_x000D_
Painless, slow growing mass, usually in body or tail_x000D_
Filled with thick, tenacious mucin, lined by columnar mucin producing epithealial cells_x000D_
Associated with dense 'ovarian like' stroma_x000D_
1/3 harbor associated invasive adenocarcinoma |
|
|
Term
| Pancreatic Solid Cystic Pseudopapillary Neoplasm |
|
Definition
Large well circumscribed masses with solid and cystic components_x000D_
Cystic areas filled with hemorrhagic debris - neoplastic cells grow in papillary projections_x000D_
Most contain activating mutations of beta catenin_x000D_
May present with abdominal discomfort due to large size_x000D_
Some are locally aggressive - most are completely benign |
|
|
Term
| Pancreatic Intraductal Papillary Mucinous Neoplasm |
|
Definition
Mucin producing intraductal neoplasm - connect to pancreatic duct systm_x000D_
Frequently involve head of pancreas, may be multifocal_x000D_
Lack dense 'ovarian like' stroma seen in mucinous cystic neoplasm_x000D_
May be benign or malignant - determined by tissue invasion on biopsy_x000D_ |
|
|
Term
| Pancreatic Acinar Cell Carcinoma |
|
Definition
Neoplastic lesion with acinar cell differentiation - zymogen granules, exocrine enzymes_x000D_
Significant malignant potential - lack KRAS and p53 mutations like ductal adenocarcinoma_x000D_
Can develop metastatic fat necrosis due to release of lipase into circulation |
|
|
Term
|
Definition
Strawberry Gallbladder_x000D_
Cholesterol laden macrophages in lamina propria of gallbladder mucosa_x000D_
No clinical significance or relationship to systemic lipid disorder |
|
|
Term
| Acute Cholecystitis - Pathogenesis _x000D_ |
|
Definition
Acute inflammation of gallbladder - 90% due to obstruction of biliary tree by gallstones_x000D_
Mucosal phospholipases hydrolyze luminal bile lecithins to toxin lysolecithins_x000D_
Protective glycoprotein mucous layer is disrupted - direct detergent effects of bile on mucosa_x000D_
Wall distension releases prostaglandins --> acute inflammatory infiltrate_x000D_
Gallbladder dysmotility, increased intraluminal pressure --> compromised blood flow |
|
|
Term
| Acute Acalculous Cholecystitis |
|
Definition
Acute inflammation of gallbladder without obstruction by gallstone - 10% of acute cholecystitis cases_x000D_
Caused by ischemia of cystic artery - no collateral circulation_x000D_
Occurs in ill hospitalized patients with risk factors for vascular disease_x000D_
Can be initiated by primary bacterial infection_x000D_
Higher incidence of gangrenous cholecystitis and perforation than calculous causes |
|
|
Term
| Acute Cholecystitis - Clinical Presentation |
|
Definition
Acute right upper quadrant or epigastric pain_x000D_
Mile fever, anorexia, tachycardia, sweating, nausea, vomiting_x000D_
Hyperbilirubinemia but infrequently jaundice - mild elevation of alkaline phosphatase serum levels |
|
|
Term
| Acute Cholecystitis - Morphology and Histology |
|
Definition
Gallbladder is enlarged and tense_x000D_
Subserosal hemorrhages, fibrin coat, suppurative coagulated exudate_x000D_
Wall thickened by edema, congestion, hemorrhage, and inglammation_x000D_
Neutrophilic infiltration |
|
|
Term
| Chronic Cholecystitis - Pathogenesis |
|
Definition
Can be caused by repeated attacks of acute cholecystitis_x000D_
May develop without preceding acute attacks _x000D_
No direct role for gallstones - obstruction of bile outflow not required_x000D_
Supersaturation of bile predisposes to chronic inflammation and gall stones independently_x000D_
Chronic inflamatory infiltrate, subserosal fibrosis |
|
|
Term
| Chronic Cholecystitis - Clinical Presentation |
|
Definition
Recurrent attacks of steady or colicky right upper quadrant or epigastric pain_x000D_
Nausea, vomiting, intolerance for fatty foods |
|
|
Term
| Chronic Cholecystitis - Morphology and Histology |
|
Definition
Thickened wall due to muscular hypertrophy and firbrosis_x000D_
Infiltrate of lymphocytes, plasma cells, macrophages_x000D_
Subepithelial and subserosal fibrosis_x000D_
Rokitansky Aschoff sinuses - outpouchings of mucosal epithelium through wall of gallbladder |
|
|
Term
| Rokitansky Aschoff Sinuses |
|
Definition
Outpouchings of mucosal epithelium through wall of gallbladder_x000D_
Seen in chronic cholecystitis |
|
|
Term
| Cholecystitis - Complications |
|
Definition
Bacterial superinfection with cholangitis or sepsis_x000D_
Gallbladder perforation and local abscess formation_x000D_
Gallbladder rupture with diffuse peritonitis_x000D_
Biliary enteric fistula - drainage of bile into adjacent organs, entry of air and bacteria into biliary tree_x000D_
Aggravation of preexisting conditions - pulmonary, renal, or liver decompensation |
|
|
Term
|
Definition
Severe complication of acute cholecystitis_x000D_
Gallbladder necrosis and perforation_x000D_
Invasion of gas forming organisms - clostridia and coliforms - can cause acute emphysematous cholecystitis_x000D_
More common in acalculous cholecystitis in severely ill patients |
|
|
Term
|
Definition
Extensive dystrophic calcification within the gall bladder wall_x000D_
Increased incidence of associated cancer_x000D_
Occurs in rare cases of chronic cholecystitis |
|
|
Term
| Laboratory Evaluation of Hepatocyte Integrity |
|
Definition
Serum Aspartate Aminotransferase (AST)_x000D_
Serum Alanine Aminotransferase (ALT)_x000D_
Elevated values indicate liver disease_x000D_
Serum Lactate Dehydrogenase (LDH) less commonly used |
|
|
Term
| Laboratory Evaluation of Biliary Excretory Function |
|
Definition
Serum bilirubin, urine bilirubin, and and serum bile acids - normally secreted in bile_x000D_
Serum Alkaline Phosphatase, Serum GGT - bile canaliculus plasma membrane enzymes_x000D_
Elevated values indicate liver disease |
|
|
Term
| Laboratory Evaluation of Hepatocyte Function |
|
Definition
Serum albumin - secreted by hepatocytes - decreased levels indicate liver disease_x000D_
Prothrombin time - mediated by coagulation factors secreted by hepatocytes - elevated time indicates liver disease_x000D_
Serum Ammonia - hepatocyte metabolism - elevated levels indicate liver disease |
|
|
Term
|
Definition
Liver encapsulation - contains nerve fibers activated by rapid stretching and signaling pain_x000D_
Posterior bare area under diaphragm only part not covered by peritoneum |
|
|
Term
| GI - Embryonic Bile Duct Development |
|
Definition
Hepatic diverticulum from endodermal foregut lining_x000D_
Caudal portion differentiates into gallbladder and extrahepatic ducts_x000D_
Cranial portion differentiates into hepatic cords_x000D_
Hepatoblasts adjacent to portal vein induced to differentiate into bile duct cells by Jag1/Notch signaling_x000D_
Ring of bile duct precursors form ring around portal vein - asymmetric apoptosis results in eccentric ring_x000D_
Oldest bile ducts located in center - youngest bile ducts located in periphery_x000D_ |
|
|
Term
|
Definition
Benign lesion - multiple bile duct structures in portal triad_x000D_
Dilated bile ducts embedded in fibrous hyalinized stroma close to or within portal tract_x000D_
May reflect failure of apoptosis |
|
|
Term
| Congenital Hepatic Fibrosis |
|
Definition
Developmental abnormality of bile duct plate_x000D_
Almost every portal tract involved by bile duct hamartoma_x000D_
Present with portal hypertension due to increased resistance in liver_x000D_
No compromise of synthetic or clearing functions |
|
|
Term
|
Definition
Developmental abnormality of bile duct development_x000D_
Multiple segmentally dilated large bile ducts_x000D_
Associated with portal tract fibrosis and congenital hepatic fibrosis_x000D_
Results in static bile and predisposes to stone formation_x000D_
Increased risk of cholangiocarcinoma |
|
|
Term
|
Definition
Autosomal dominant mutation in Jagged1 - ligand for notch regulating cell fate_x000D_
Liver pathology - absence of bile ducts in portal tracts --> chronic cholestasis_x000D_
Peripheral stenosis of pulmonary artery, butterfly like vertebral arch defect_x000D_
Posterior embryotoxon eye defect, hypertelic facies_x000D_
Risk for hepatic failure and hepatocellular carcinoma |
|
|
Term
|
Definition
Single blood supply from hepatic artery_x000D_
Hepatic artery forms plexus around bile duct |
|
|
Term
| Liver - Vasculature Supply and Drainage |
|
Definition
Portal vein provides 60-70% of nutrient rich deoxygenated blood from abdominal GI tract_x000D_
Hepatic artery provides 30-40% of oxygenated blood _x000D_
Portal tracts --> sinusoids --> central veins --> hepatic veins_x000D_
Three hepatic veins from Right, Left, and Quadrate lobe fuse to form Hepatic Vein that feeds into IVC_x000D_
Caudate lobe has separate venous drainage into IVC |
|
|
Term
|
Definition
Obstruction of 2+ major hepatic veins --> acute venous outflow obstruction _x000D_
Liver enlargement, swollen and red with tense capsule, pain, portal hypertension and ascites_x000D_
Nutmeg appearance - alternating red congestion with lighter areas_x000D_
Hepatic damage from increased intrahepatic blood pressure_x000D_
Severe centrolobular (zone 3) congestion and necrosis_x000D_
Caudate lobe is spared - separate drainage - hypertrophies with chronic obstruction_x000D_ |
|
|
Term
| Budd Chiari Syndrome - Etiology |
|
Definition
Hypercoagulable states_x000D_
Primary myeloproliferative disorders_x000D_
Antiphospholipid syndrome_x000D_
Paroxysmal nocturnal hemoglobinuria_x000D_
Intra-abdominal cancers - hepatocellular carcinoma_x000D_
Pregnancy or use of oral contraceptices |
|
|
Term
| Veno Occlusive Disease / Sinusoidal Obstruction Syndrome |
|
Definition
Toxic injury to sinusoidal endothelium - embolization of damaged cells and occlusion of central vein_x000D_
Congestion and necrosis of perivenular hepatocytes, accumulation of debris in terminal hepatic vein_x000D_
Increased pressure causes fibrosis and collagen matrix deposition in sinusoids_x000D_
Obliteration of hepatic vein radicles_x000D_
Results from EtOH, Jamaican bush tea, chemotherapy drugs, bone marrow transplant drugs |
|
|
Term
| Liver Response to Outflow Obstruction |
|
Definition
Chronic increased pressure induces collagen matrix deposition and venous sclerosis_x000D_
Pressure atrophy results in loss of hepatocytes_x000D_
Increased resistance --> portal hypertension --> ascites_x000D_
If due to hepatic vein obstruction --> caudate lobe sparing and hypertrophy_x000D_
If due to cardiac or pulmonary pressure --> no sparing of caudate lobe_x000D_ |
|
|
Term
|
Definition
May lead to Stellate / Ito cell swelling in space of Disse_x000D_
Can block sinusoid blood flow leading to liver swelling and portal hypertension_x000D_
Chronic Vitamin A overload causes Ito cells to deposit collagen leading to cirrhosis |
|
|
Term
|
Definition
Rare - dual blood supply - branch of hepatic artery can be occluded by embolism, neoplasm, PAD, or sepsis_x000D_
Ischemia results in coagulative necrosis of hepatocytes surrounded by transition zone of reversibly damages cells_x000D_
Necrotic area surrounded by hyperemic rim_x000D_
No fibrosis from ischemia |
|
|
Term
|
Definition
Occlusive disease may progress over time - usually no acute effect_x000D_
Abdominal pain, portal hypertension, esophageal varices_x000D_
Vein remodeling and collagen deposition around vein_x000D_
Impaired regeneration due to loss of growth factors delivered by portal vein_x000D_
No fibrosis of hepatic parenchyma |
|
|
Term
| Liver - Cardiac Sclerosis |
|
Definition
Right sided cardiac failure --> passive congestion of liver_x000D_
Centrolobular congestion and atrophy_x000D_
Left sided cardiac failure --> shock, hypotension --> hepatic hyoperfusion and hypoxia_x000D_
Centrolubular ischemic coagulative necrosis_x000D_
Hemorrhage and necrosis --> nutmeg liver |
|
|
Term
| LFT - Alanine Aminotransferase (ALT) |
|
Definition
Liver cytoplasm restricted enzyme - present in hepatocytes_x000D_
Acute hepatocyte damage releases ALT into serum - viral hepatitis or acetaminophen overdose_x000D_
Upper Limit of Normal = 40 IU/L |
|
|
Term
| LFT - Aspartate Transaminase (AST) |
|
Definition
Enzyme present in hepatocytes - also in heart, skeletal muscle, kidney, brain, pancreas, spleen, and lung_x000D_
Located in cytoplasm and mitochondria - _x000D_
Mitochondria specific insult will be reflected by AST > ALT - EtOH, Wilson's_x000D_
Upper Limit or Normal = 35 IU/L |
|
|
Term
| LFT - Gamma Glutamyl Transpeptidase (GGT) |
|
Definition
Liver enzyme located in bile canaliculus membrane_x000D_
Elevated serum levels indicate damage to biliary tree, bile duct obstruction, cholestasis, or inflitrative disease_x000D_
Upper Limit of Normal = 42 IU/L |
|
|
Term
| LFT - Alkaline Phosphatase (ALP) |
|
Definition
Liver enzyme located in bile canaliculi - also in bone and placental tissue_x000D_
Elevated serum levels indicate damage to biliary tree, bile duct obstruction, cholestasis, or inflitrative disease_x000D_
Levels will be low in Wilson's, hypothyroidism, and congenital hypophosatasia_x000D_
Upper Limit of Normal = 120 IU/L |
|
|
Term
|
Definition
Hepatic Damage - Elevated ALT, normal AP and Bilirubin_x000D_
Cholestatic - Normal ALT, elevated AP, elevated Bilirubin_x000D_
Infiltrative - Normal ALT, elevated AP, normal Bilirubin |
|
|
Term
| LFT - DDx for Transaminases > 1000 |
|
Definition
Autoimmune hepatitis_x000D_
Viral hepatitis - B most common, C rare_x000D_
Fulminant Wilson's_x000D_
Toxins - acetaminophen_x000D_
Budd Chiari_x000D_
Shock |
|
|
Term
| Liver Injury - Hepatic Pattern |
|
Definition
ALT and AST elevation with no elevation of AP, GGT, or Bilirubin_x000D_
Portal tracts infiltrated with lymphocytes and plasma cells_x000D_
Hepatocytes can die by apoptosis, necrosis, ballooning degeneration, or cholestasis _x000D_
Causes - Hep C, autoimmune hepatitis |
|
|
Term
| Liver Injury - Hepatocyte Apoptosis |
|
Definition
Mediated by Fas pathway_x000D_
Response from cytotoxic cell injury_x000D_
Results in elevated ALT/AST, normal GGT, AP, and Bilirubin |
|
|
Term
|
Definition
Hepatocytes engulfed with neutral lipids - appears as white vacuole_x000D_
Occurs in diabetes, obesity, and EtOH ingestion_x000D_
Mild elevation of ALT/AST and/or GGT/AP, normal bilirubin |
|
|
Term
| Liver Injury - Cholestatic |
|
Definition
Bile plugs composed of bilirubin becomes trapped between hepatocytes_x000D_
Delta-bilirubin in serum, first seen in zone 3 _x000D_
Extremely elevated AP/GGT, elevated bilirubin, slightly elevated ALT/AST_x000D_
Causes - gallstone, tumor, drugs, gram negative bacterial sepsis |
|
|
Term
|
Definition
End product of heme degradation - 80% from RBC / 20% from hepatic heme or hemoproteins_x000D_
Heme --(Heme Oxygenase)--> Fe + CO + Biliverdin --(Biliverdin Reductase)--> Bilirubin_x000D_
Bilirubin transported to liver hydrogen bonded to albumin - carrier mediate uptake at sinusoidal membrane_x000D_
Conjugation with glucaronic acid in ER and excretion into bile |
|
|
Term
|
Definition
Yellow discoloration of skin (jaundice) and sclera (icterus)_x000D_
Occurs when serum bilirubin is 2x the Upper Limit of Normal_x000D_ |
|
|
Term
|
Definition
Unconjugated bilirubin is toxic to CNS - especially newborn_x000D_
Polar proprionic acid groups hidden internally in bilirubin structure --> water insolbule_x000D_
Addition of glucuronide by UDP glucuronosyltransferase in ER _x000D_
Opens molecule, exposes proprionic acid groups --> water soluble and excretable_x000D_
Light exposure can break internal hydrogen bonds and make unconjugated bilirubin water soluble_x000D_
Deconjugated in GI lumen by bacterial glucuronidases and degraded to colorless urobilinogens |
|
|
Term
|
Definition
Bilirubin secreted into canaliculus against concentration gradient - rate limiting_x000D_
Separate ATP dependent transporters for phospholipids and bile salts_x000D_
66% bile salts, 22% phospholipid, 5% cholesterol, 5% protein, 1% bilirubin |
|
|
Term
| Bilirubin - Delta Bilirubin |
|
Definition
Conjugated bilirubin covalently bound to albumin_x000D_
Found in serum of patients with conjugated hyperbilirubinemia_x000D_
Indicates obstruction of bile secretion, build up in hepatocyte and backflow into serum_x000D_
Covalent bond prevents dissociation at hepatocyte membrane_x000D_
Albumin binding prevents excretion in urine and prolongs half life |
|
|
Term
|
Definition
GI bacteria deconjugate bilirubin to colorless water soluble urobilogen_x000D_
Bacteria then convert urobilogen to pyrroles --> stool coloration |
|
|
Term
|
Definition
Unconjugated hyperbilirubinemia - hydrogen bonding to albumin prevents passage into urine_x000D_
Conjugated hyperbilirubinemia - water soluble conjugated bilirubin passes into urine_x000D_
Urine dipstick test for bilirubin distinguishes unconjugated from conjugated _x000D_
Delta bilirubin convalently bound to albumin cannot pass into urine |
|
|
Term
| Unconjugated Hyperbilirubinemia - Causes |
|
Definition
Overproduction - hemolytic anemia, ineffective erythropoiesis, internal hemorrhage_x000D_
Reduced uptake - drugs (rifamycin), portasystemic shunting_x000D_
Impaired conjugation - Crigler Najjar Syndromes, Gilbert's Syndrome, |
|
|
Term
| Physiologic Jaundice of the Newborn |
|
Definition
Hepatic machinery for conjugating and excreting bilirubin not fully mature until 2 weeks post natal_x000D_
Most newborns develop mild transient unconjugated hyperbilirubinemia_x000D_
Deconjugating enzymes in breast milk can exacerbate jaundice with breast feeding_x000D_
Sustained jaundice longer than two weeks suggests neonatal cholestasis_x000D_ |
|
|
Term
|
Definition
| Accumulation of unconjugated bilirubin in the brain --> neurologic damage |
|
|
Term
|
Definition
Type 1 - complete absence of hepatic UGT1A1 --> inability to conjugate bilirubin_x000D_
Severe unconjugated hyperbilirubinemia, jaundice, and icterus_x000D_
Fatal < 18 months due to kernicterus without liver transplant_x000D_
Type 2 - reduced activity of UGT1A1 --> can only monoglucuronidate bilirubin_x000D_
Very yellow skin is only major consequence_x000D_
Phenobarbital treatment can cause hypertrophy of hepatocellular ER and improve function |
|
|
Term
|
Definition
Common benign inherited condition _x000D_
Mutations in promoter of UGT1 reduce transcription --> 30% activity of conjugation system_x000D_
Mild fluctuating unconjugated hyperbilirubinemia, normal LFT, no bilirubin in urine _x000D_
Clinically benign - may be more susceptible to adverse effects of drugs, fasting may cause jaundice_x000D_ |
|
|
Term
| Conjugated Hyperbilirubinemia - Causes |
|
Definition
Inherited - Dubin Johnson and Rotor Syndromes_x000D_
Acquired - cholestatic and necrotizing hepatocellular injury_x000D_
Injury to cell or biliary obstruction causes reflux into serum |
|
|
Term
| Dubin Johnson and Rotor Syndromes |
|
Definition
DJ - chronic conjugated hyperbilirubinemia - defect of MDRP2 - excretes bilirubin across canicular membrane_x000D_
Rotor - chronic conjugated hyperbilirubinemia - defects of uptake and excretion of bilirubin pigments_x000D_
Asymptomatic except for jaundice |
|
|
Term
|
Definition
Pathologic impaired bile formation and bile flow --> bile pigment accumulation in hepatic parenchyma_x000D_
Can be caused by extrahepatic or intrahepatic obstruction or defects in secretion_x000D_
Jaundice, pruritus, skin xanthomas, and deficiencies of fat soluble vitamins_x000D_
Characteristic elevation of Alk Phos and GGT |
|
|
Term
| Cholestasis - Morphology and Histology |
|
Definition
Accumulation of bile pigment within hepatic parenchyma_x000D_
Elongated green/brown bile plugs in dilated bile canaliculi - distension of upstreatm ducts_x000D_
Bile extravasation and phagocytosis by kupffer cells_x000D_
Accumulation in hepatocytes --> fine foamy appearance --> feathery degeneration_x000D_
Portal tract edema, neutrophilic infiltrate_x000D_
Dissolution of hepatocytes by bile detergent --> bile lakes_x000D_ |
|
|
Term
| Cholestasis - Biochemical Findings |
|
Definition
Elevated Alk Phos and GGT_x000D_
Increased synthesis of canicular Alk Phos in response to increased pressure_x000D_
Elevated bilirubin |
|
|
Term
| Cholestasis - Extrahepatic Causes |
|
Definition
Obstruction_x000D_
Benign - gallstones, strictures, pancreatitis_x000D_
Malignant - cancer of pancreas, bile duct, or gallbladder |
|
|
Term
| Cholestasis - Intrahepatic Causes |
|
Definition
At Hepatocyte - EtOH, drugs, Hep A, sepsis, TPN_x000D_
At Canaliculus - Pregnancy, estrogen, drugs_x000D_
At Bile Duct - TB Granulomatous, Primary Biliary Cirrhosis, Primary Sclerosing Cholangitis |
|
|
Term
| Bilirubin - Maximum Serum Levels |
|
Definition
30-35 mg/dl is maximum amount possible from isolated obstruction_x000D_
Urine clearance matches amount generated from hemoglobin degradation_x000D_
Can exceed 30-35 if simultaneous hemolysis or renal failure occurs with obstruction |
|
|
Term
|
Definition
Cholesterol stones - form in gallbladder_x000D_
Black pigment stones - mainly unconjugated bilirubin - form in gallbladder_x000D_
Brown pigment stones - mainly unconjugated bilirubin - form in bile duct |
|
|
Term
|
Definition
Supersaturation of bile with cholesterol or bilirubin_x000D_
Stasis of bile_x000D_
Mucous hypersecretion promotes crystal nucleation_x000D_
Cholesterol and Black stones form in gallbladder, brown stones form in bile duct |
|
|
Term
|
Definition
50-90% cholesterol, 5-10% mucin, small amounts of calcium salts_x000D_
Risk factors - female, fat, fertile, forty (4F)_x000D_
Cholesterol supersaturation compared to relatively low bile salts and phospholipids_x000D_
Gallbladder stasis promotes nucleation and is accelerated by mucous hypersecretion_x000D_
Treated with ursodeoxy and chenodeoxycholic acid - not effective in pigment stones_x000D_
Appear radiolucent - increasing amounts of calcium carbonate makes them radiopaque |
|
|
Term
|
Definition
Form in sterile gallbladder bile_x000D_
Abnormal insoluble calcium salts and unconjugated bilirubin_x000D_
Calcium phosphates and carbonates --> radiopaque_x000D_
Associated with elderly, hemolytic anemia, and cirrhosis |
|
|
Term
|
Definition
Form in bile duct associated with bacterial infection_x000D_
Bacteria deconjugate bilirubin in duct_x000D_
Radiolucent due to calcium soaps and minimal calcium salts |
|
|
Term
| Gallstones - Clinical Features |
|
Definition
Most asymptomatic_x000D_
Biliary pain, constant or colicky, radiate to right shoulder_x000D_
Complications include empyema, perforation, fistulas, cholangitis, obstructive cholestasis_x000D_
Smaller stones can travel through ducts and become trapped in common ducts_x000D_
Increased risk for gallbladder carcinoma |
|
|
Term
| Biliary Atresia - Overview |
|
Definition
Complete or partial obstruction of lumen of extrahepatic biliary tree w/ 3 months neonatal_x000D_
Progressive inflammation and fibrosis of bile ducts_x000D_
Fetal form - abnormal development, associated with polysplenia and other developmental anomalies_x000D_
Perinatal form - normal development, inflammatory destruction, viral trigger? |
|
|
Term
| Biliary Atresia - Clinical Features |
|
Definition
Neonatal cholestasis - normal birth weight and post natal weight gain_x000D_
Initially normal stools become acholic_x000D_
Serum conjugated bilirubin > 6-12, moderately elevated ALT, elevated AP and GGT_x000D_
Diagnose with operatice cholangiogram, ultrasound or Disida scintiscan - radio tracer taken up and excreted by liver_x000D_
Biopsy shows bile duct proliferation, ductal bile plugs, and portal fibrosis |
|
|
Term
| Biliary Atresia - Treatment |
|
Definition
Kasai hepatoportoenterostomy - surgical resection and bypass of biliary tree_x000D_
Limited by intrahepatic progression of disease, bacterial contamination and experience of surgeon_x000D_
More effective when performed at younger age_x000D_
Only possible for 10% of cases that don't involve bile ducts above porta hepatis_x000D_
Transplantation is only cure |
|
|
Term
| Metabolic Liver Disease - Hepatic Presentations |
|
Definition
Hepatomegaly - Glycogen storage disease, defective breakdown, present with hypoglycemia_x000D_
Hepatosplenomegaly - Niemann Pick disease, abnormal lipid accumulation in reticuloendothelial cells_x000D_
Liver Failure - Tyrosinemia, toxic metabolites cause liver damage_x000D_
Cholestasis - cystic fibrosis |
|
|
Term
| Inherited Causes of Cirrhosis - Pediatrics v Adults |
|
Definition
Peds - A1AT 50% of cases, Hemochromatosis rare_x000D_
Adults - Hemochromatosis 75% of cases |
|
|
Term
| Alpha 1 Antitrypsin Deficiency - Overview |
|
Definition
Autosomal recessive deficiency in A1AT - low serum levels and impaired subcellular trafficking_x000D_
Synthesized by Liver - functions to inhibit neutrophil elastase in lung --> protects from inflammatory damage_x000D_
Early onset emphysema +/- Liver disease_x000D_
Z allele misfolds and accumulates in hepatocyte ER inducing damage_x000D_
Affected patients may have underlying impairment in protein trafficking --> susceptible to accumulation_x000D_
Presents with neonatal hepatitis and cholestatic jaundice or later with hepatitis or cirrhosis |
|
|
Term
| Alpha 1 Antitrypsin Deficiency - Treatment |
|
Definition
Avoid cigarette smoking, treat complications, screen for hepatocellular carcinoma_x000D_
May require liver or lung transplantation_x000D_
Carbamazepine may be used to enhance autophagy and increase clearance of accumulated protein |
|
|
Term
| Alpha 1 Antitrypsin Deficiency - Histology |
|
Definition
Round cytoplasmic globular inclusions in hepatocytes_x000D_
Acidophilic, stain strongly with PAS |
|
|
Term
| Wilson Disease - Normal Copper Metabolism |
|
Definition
Ingested Cu is absorbed in duodenum and proximal intestine - transported to Liver_x000D_
Taken up by hepatocytes, incorporated into apoceruloplasmin to form ceruloplasmin, and excreted into bile_x000D_
Ceruloplasmin circulates in blood before being taken up by liver, degraded, and Cu eliminated in bile_x000D_
ATP7B - Cu transporting ATPase, required to excrete into bile and incorporate into ceruloplasmin |
|
|
Term
| Wilson Disease - Pathophysiology |
|
Definition
Autosomal recessive deficiency in ATP7B - Cu transporting ATPase_x000D_
Decreased Cu excretion into bile, incorporation into ceruloplasmin, and secretion of ceruloplasmin into blood_x000D_
Cu accumulation in liver --> ROS production --> toxic liver injury_x000D_
Hemolysis, deposition in Descemet's membrane in eye and basal ganglia_x000D_
Treat with Cu chelating agents or Zinc therapy_x000D_ |
|
|
Term
|
Definition
Green to brown deposits of Cu in Descemet's membrane in the limbus of the cornea_x000D_
Visible under slit lamp exam_x000D_
Occurs in almost all patients with Wilson's Disease |
|
|
Term
| Wilson Disease - Clinical Presentation |
|
Definition
Acute or chronic liver disease - hepatic symptoms present earlier than neurologic symptoms _x000D_
Neurologic changes - parkinson like syndrome, rigidity, tremors, gait, choreiform _x000D_
Kayser Fleischer rings - visible under slit lamp exam_x000D_
Decreased serum ceruloplasmin, increased hepatic Cu (sensitive), increased urinary Cu (specific_x000D_
May be silent until sudden onset of critical systemic illness_x000D_
Elevated ALT/AST but LOW ALK PHOS |
|
|
Term
| Hemochromatosis - Iron Metabolism |
|
Definition
Iron levels regulated by intestinal absorption via Hepcidin - no regulated excretion_x000D_
Hepcidin binds to ferroportin on intestinal cells, internalizes it to prevent release of iron from intestinal cells_x000D_
Hepcidin transcription is increased by inflammation and iron_x000D_
Hepcidin transcription is decreased by iron deficiency, hypoxia, and ineffective erythropoiesis_x000D_
Hepcidin deficiency results in iron overabsorption_x000D_
Hepcidin regulated by HJV, TfR2, and HFE |
|
|
Term
| Hereditary Hemochromatosis - Pathophysiology |
|
Definition
Deficiency in Hepcidin via hepcidin mutation or mutation in HJV, TfR2, or HFE that regulate Hepcidin_x000D_
Excessive accumulation of iron - deposition in liver, pancreas, heart, joints, and endocrine organs_x000D_
Increased enteral absorption --> early hemosiderin deposition in Zone 1 hepatocytes _x000D_
Iron causes lipid peroxidation via free radical reactions, stimulates stellate cell collagen deposition_x000D_
Iron generates ROS and directly interacts with DNA causing lethal cell injury - increased risk of HCC |
|
|
Term
| Hereditary Hemochromatosis - Clinical Features |
|
Definition
Classic triad of hepatomegaly, diabetes mellitus, and skin pigmentation_x000D_
Death from cardiac disease and cirrhosis progressing to hepatocellular carcinoma_x000D_
Arthralgias, cardiac disease, infections_x000D_
Abdominal pain, weakness, lethargy, impotence, gynecomastia, testicular atrophy, splenomegaly_x000D_
Diagnose with high levels of serum iron and ferritin and with liver biopsy _x000D_
Hemosiderin deposition in Zone 1 hepatocytes - if from transfusion, will deposit in Kupffer cells_x000D_
Treat with phlebotomy_x000D_ |
|
|
Term
| Hereditary Hemochromatosis - HFE |
|
Definition
Most common mutation in adult hemochromatosis_x000D_
Intestinal epithelial cell senses iron levels in body based on intracellular iron pool_x000D_
Uptake of iron bound to transferrin carrier regulated by HFE determines intracellular pool_x000D_
Body levels of iron indicated by levels of transferrin - synthesis in liver stimulated by low iron / ferritin_x000D_
Mutated HFE results in false detection of high transferrin levels_x000D_
Interpreted as low serum iron --> increased intestinal absorption of iron |
|
|
Term
| Alcoholic Liver Disease - Alcohol Metabolism |
|
Definition
Low levels - EtOH --(ADH)--> Acetaldehyde --(ALDH)--> Acetate (+ 2 NAD+ --> 2 NADH)_x000D_
High levels - EtOH --(MEOS)--> Acetaldehyde --(Oxidases)--> Acetate (+ 2 reactive oxygen species) |
|
|
Term
| Alcoholic Liver Disease - Steatosis Pathogenesis |
|
Definition
Short term EtOH ingestion results in mild reversible hepatic steatosis_x000D_
Generation of NADH via alcohol dehydrogenase and acetaldehyde dehydrogenase_x000D_
Results in increased Fatty acid synthesis, decreased fatty acid oxidation, and impaired secretion of lipoproteins_x000D_
Fatty acids accumulate, are esterified, and stored as triglycerides in hepatocytes_x000D_
Microvesicular lipid droplets - compress and displace nuclei |
|
|
Term
| Alcoholic Liver Disease - Hepatitis Pathogenesis |
|
Definition
Acetaldehyde and free radicals induce lipid peroxidation_x000D_
Decreased glutathione (requires NAD+ to regenerate) sensitizes liver to oxidative injury_x000D_
Induction of CYP2E1 enhances oxidation metabolism of other drugs_x000D_
Alcohol induces release of bacterial endotoxins into portal circulation --> inflammatory response_x000D_
Alcohol induces release of endothelins from sinusoid --> vasoconstricion and stellate cell activation |
|
|
Term
| Alcoholic Liver Disease - Steatosis Clinical Features_x000D_ |
|
Definition
Tender hepatomegaly, non specific symptoms of fatigue, malaise, anorexia, abdominal discomfort_x000D_
Mild elevation of bilirubin, Alk Phos, and ALT/AST_x000D_
Macrovesicular steatosis seen on histology_x000D_
More commonly seen with chronic abuse |
|
|
Term
| Alcoholic Liver Disease - Hepatitis Clinical Features |
|
Definition
Jaundice, splenomegaly, palmar erythema, asterixis, ascites_x000D_
AST > ALT (2:1), increased prothrombin time_x000D_
Macrovesicular steatosis, neutrophil infiltrate, centrilobular swelling, ballooning degeneration, mallory bodies_x000D_
Severe --> portal hypertension --> esophageal varices, ascites, hepatic encephalopathy _x000D_
Malnutrition from calorie displacement _x000D_
Appear in chronic drinker after acute ingestion of large amounts of EtOH_x000D_ |
|
|
Term
|
Definition
Accumulations of ubiquinated intermediate filaments in hepatocytes_x000D_
Appear as eosinphilic cytoplasmic clumps_x000D_
Seen in alcoholic liver disease - also in NAFLD, PBC, Wilsons, cholestatic syndromes, and hepatocellular tumors |
|
|
Term
| Alcoholic Liver Disease - Mortality |
|
Definition
Hepatic coma, massive GI bleed, infection, hepatorenal syndrome, hepatocellular carcinoma_x000D_
Good prognosis if abstain from EtOH_x000D_
Signs of decompensation reflect poorer prognosis |
|
|
Term
| Non Alcoholic Fatty Liver Disease - Overview |
|
Definition
Hepatic steatosis with no history of alcohol abuse_x000D_
Includes seatosis, NASH (steatohepatitis), and Cirrhosis_x000D_
Risk factors - obesity, hyperglycemia, T2D, hypertriglyceridemia_x000D_
Metabolic Syndrome - obesity, high TG, low HDL, elevated BP and fasting plasma glucose_x000D_ |
|
|
Term
| Non Alcoholic Fatty Liver Disease - Pathogenesis |
|
Definition
Combination of insulin resistance and hepatocyte oxidative stress_x000D_
IR --> increased peripheral lipolysis + hyperinsulinemia --> hepatic fat accumulation_x000D_
Hyperinsulinemia --> increases glycolysis and de novo fatty acid synthesis, decreased apo B100 and VLDL export_x000D_
FFA upregulate hepatocyte p450 enzymes --> oxidative stress_x000D_
Hepatic fat accumulation --> oxidative stress --> lipid peroxidation --> ROS --> Hepatocyte damage |
|
|
Term
| Non Alcoholic Fatty Liver Disease - Clinical Features |
|
Definition
AST:ALT is less than 3:1 - commonly > 3:1 in alcoholic steatohepatitis_x000D_
Fatigue, right sided abdominal discomfort, cardiovascular comorbidity |
|
|
Term
| Non Alcoholic Fatty Liver Disease - Treatment |
|
Definition
Weight reduction and correction of central obesity_x000D_
Insulin sensitizing agents - rosiglitazone/pioglitazone - may worsen obesity_x000D_
Antioxidants - vitamin E,C, Betaine |
|
|
Term
| Vitamin C Deficiency - Clinical Features |
|
Definition
Required for hydoxylation of proline and lysine on collage, antioxidant activity, increases iron absorption_x000D_
Impaired collagen formation - poor blood vessel strength, inadequate osteoid synthesis, impaired wound healing_x000D_
Pain and extremity weakness in children_x000D_
Erythema on gingica, buccal ulcers, hard palate lesions_x000D_
Petechia and bruises, eczema flare, microcytic anemia_x000D_
Cork screw hemorrhagic hair follicles |
|
|
Term
| Rickets - Clinical Features |
|
Definition
Vitamin D deficiency_x000D_
Hypotonia and muscle weakness_x000D_
Tetany and seizures_x000D_
Bone pain, decreased linear growth_x000D_
Bone and cartilage deformities_x000D_
Respiratory infections |
|
|
Term
| Rickets - Pathophysiology |
|
Definition
Vit D Deficiency --> Secondary Hyperparathyroidism --> Phosporus Deficiency_x000D_
PTH stimulates Ca reabsorption, renal Vit D activation, and bone remodelling_x000D_
Elevated serum Ca and Urinary Phosphate Excretion_x000D_
Transient increase in Pi absorption --> FGF23 release --> increased Pi excretion_x000D_
Return low Ca levels to normal at expense of phosphorus |
|
|
Term
| Rickets - Biochemical Status |
|
Definition
Low serum Ca, Low serum Pi, high Alk Phosphatase, high PTH, low 25-OH-D_x000D_
Elevated Alk Phosphatase and PTH are earliest markers_x000D_
Measure 25-OH-D when suspect nutritional rickets - reflects dietary intake_x000D_
Don't measure 1,25-OH2-D - will be misleadingly normal or high |
|
|
Term
|
Definition
Photochemical conversion in skin of 7-dehydrocholesterol --> Vitamin D3 via UVB radiation (90%)_x000D_
Dietary - fish, plants, grains - fat soluble vitamin requires adequate fat absorption_x000D_
Transport of D3 to liver via α1-globulin_x000D_
Liver convrsion to 25-OH-D via 25-hydroxylases_x000D_
Kidney conversion to 1.25-OH2-D via α1-hydroxylase |
|
|
Term
| Vitamin D - Regulation of Renal Conversion to 1.25-OH2-D |
|
Definition
Parathyroid Hormone activates 1α-hydroxylase_x000D_
PTH released in response to hypocalcemia_x000D_
Hypophosphatemia directly activates 1α-hydroxylase_x000D_
Increased levels of 1,25-OH2-D feedback to inhibit 1α-hydroxylase |
|
|
Term
| Vitamin D - Effects of Calcium and Phosphorus Homeostasis |
|
Definition
Stimulates intestinal Ca absorption - transcription of TRPV6 Ca transport channel_x000D_
Stimulates renal Ca reabsorption - transcription of TRPV5_x000D_
Enhance expression of RANKL (w/ PTH) --> osteoclast differentiation_x000D_
Osteoclasts dissolve bone --> release Ca and Phosphorus into circulation_x000D_
Mineralization of bone |
|
|
Term
|
Definition
Associated with chronic diarrhea - decreased time for absorption or absorptive surface area_x000D_
Commonly seen in Celiac Disease_x000D_
Hair loss, red papular skin rash, diarrhea_x000D_
Impaired growth, developmental delay, impaired wound healing_x000D_
Treat with Zinc supplementation and gluten free diet |
|
|
Term
|
Definition
Congenital dilation of common bile duct_x000D_
Results in true diverticuli and dilation of ducts_x000D_
Predispose to stone formation, stenosis, stricture, pancreatitis, and obstructive biliary complications_x000D_
May present with jaundice and biliary colic pain --> mechanical obstruction_x000D_
Increased risk to develop adenocarcinoma |
|
|
Term
|
Definition
Develop from adenoma precursor dysplastic lesion_x000D_
95% are adenocarcinoma - 5% are squamous cell carcinoma_x000D_
Gallstones are most important risk factor_x000D_
Non specific symptoms - abdominal pain, jaundice, anorexia, nausea and vomiting_x000D_
Most have spread to liver by time of detection |
|
|
Term
|
Definition
Malignancy of biliary tree - can be intrahepatic or extrahepatic_x000D_
Klatskin tumor - perihilar tumor at junction of right and left hepatic duct_x000D_
Hilar and distal tumors present with biliary obstruction, cholangitis, and RUQ pain_x000D_
Intrahepatic tumors not detected until late in course_x000D_
Associated with primary sclerosing cholangitis, ulcerative colitis, caroli disease, choleodochal cysts_x000D_ |
|
|
Term
|
Definition
Bacterial infection of bile duct - enter through sphincter of oddi, ascending infection_x000D_
Results from obstructed bile flow - choledocholithiasis and biliary strictures_x000D_
Enteric gram negative aerobes - E coli, Klebsiella, interococcus, enterobacter, clostridium, and bacterioides_x000D_
Presents with fever, chills, abdominal pain, jaundice, neutrophil infiltration - sepsis |
|
|
Term
|
Definition
Presence of stones within the bile duct of biliary tree (cholethiasis is stones in gall bladder)_x000D_
Asymptomatic or symptoms from obstruction, pancreatitis, cholangitis, hepatic abscess, biliary cirrhosis |
|
|
Term
| Primary Biliary Cirrhosis - Overview |
|
Definition
Inflammatory autoimmune disease affecting intrahepatic bile ducts_x000D_
Nonsuppurative inflammatory destruction of medium sized intrahepatic bile ducts_x000D_
Dense infiltrate by dense accumulation of lymphocytes, macrophages, plasma cells_x000D_
Progressive destruction leads to fibrosis and cirrhosis - portal hypertension and variceal bleeding_x000D_
Presence of antimitochondrial antibody_x000D_
Associated with other autoimmune diseases_x000D_ |
|
|
Term
| Primary Biliary Cirrhosis - Biochemical Findings |
|
Definition
Elevated Alk Phos and GGT early in progression- cholestasis_x000D_
Elevated cholesterol --> eyelid xanthelasmas due to cholesterol laden macrophages_x000D_
Hyperbilirubinemia is late development - indicates ensuing hepatic decomposition_x000D_ |
|
|
Term
| Primary Biliary Cirrhosis - Pathology |
|
Definition
Aberrant expression of MHC II on bile duct epithelial cells_x000D_
Accumulation of autoreactive T cells around bile ducts_x000D_
Mitochondrial antibodies target E2 component of pyruvate dehydrogenase_x000D_
Cellular immunologic attack - biliary epithelial cell death |
|
|
Term
| Primary Biliary Cirrhosis - Treatment |
|
Definition
Ursodeoxycholic Acid_x000D_
Promotes endogenous bile acid secretion, stabilizes biliary epithelial cell membranes_x000D_
Alters bile epithelial cell HLA expression, decreases cytokine production_x000D_
Improves LFT, histologic progression, risk of decompensation, and overall survival_x000D_
No impact on symptoms |
|
|
Term
| Primary Sclerosing Cholangitis - Overview |
|
Definition
Inflammation and obliterative fibrosis of intra and extrahepatic bile ducts _x000D_
Irregular strictures and dilation of ducts - Beading seen on ERCP_x000D_
Strong association with ulcerative colitis_x000D_
Elevated GGT, Alk Phos, Bilirubin -_x000D_
Autoantibodies - P-ANCA common, No AMA (contrast with PBC)_x000D_
Increased risk of cholangiocarcinoma, chronic pancreatitis, and hepatocellular carcinoma |
|
|
Term
| Decompensated Cirrhosis - Major Complications |
|
Definition
Ascites_x000D_
Spontaneous bacterial peritonitis_x000D_
Hepatorenal syndrome_x000D_
Portosystemic shunts --> Variceal bleeding _x000D_
Hepatic encephalopathy |
|
|
Term
| Portal Hypertension - Fluid Dynamics |
|
Definition
Pressure = Flow x Resistance_x000D_
Splanchnic capillary beds are major site of flow control_x000D_
Hepatic sinusoids are main site of resistance control_x000D_ |
|
|
Term
| Portal Hypertension - Pre/Intra/Post Sinusoidal Causes |
|
Definition
Presinusoidal - obstructive thrombosis, narrowing of portal vein, splenomegaly increasing splenic vein flow_x000D_
Sinusoidal - cirrhosis, schistosomiasis, diffuse fibrosing granulomatous disease (sarcoidosis), NRH_x000D_
Postsinusoidal - right sided heart failure, constrictive pericarditis, Budd Chiari Syndrome_x000D_ |
|
|
Term
| Portal Hypertension - Pathogenesis of Increased Resistance and Flow |
|
Definition
Resistance - Sinusoidal constriction of vascular smooth muscle cells and myofibroblasts_x000D_
Disruption of blood flow by scarring_x000D_
Decreased NO and increased endothelin, angiotensinogen, and eicosanoids --> vasoconstriction_x000D_
Flow - Splanchnic arterial vasodilation stimulated by Nitric Oxide_x000D_
NO production stimulated by reduced clearance of bacterial DNA absorbed from gut due to sinusoidal pathology |
|
|
Term
| Portal Hypertension - Ascites Pathogenesis |
|
Definition
Sinusoidal hypertension drives fluid into space of Disse --> activates baroreceptors_x000D_
Reduced clearance of bacterial DNA absorbed from gut --> NO production_x000D_
NO stimulates splanchnic capillary vasodilation --> pooling of arterial blood --> reduced arterial pressure_x000D_
Activation of vasoconstrictors and activation of renin angiotensin system --> retention of sodium and water_x000D_
Extravasation of fluid into abdominal cavity |
|
|
Term
|
Definition
Serum Ascites Albumin Gradient_x000D_
Serum Albumin - Ascietes Albumin_x000D_
> 1.1 indicates portal hypertension - sinusoids intact or sclerotic_x000D_
Cirrhosis, CHF, Constrictive pericarditis, alcoholic hepatitis, Budd Chiari_x000D_
< 1.1 indicates leaky or damaged sinusoids_x000D_
Peritoneal carcinomatosis, peritoneal tuberculosis, pancreatitis, serositis, nephrotic syndrome |
|
|
Term
| Transjugular Intrahepatic Portosystemic Shunting |
|
Definition
Stent inserted to bypass blood around the liver_x000D_
Shunt from portal vein directly to hepatic vein_x000D_
Decreases resistance --> Decreases portal pressure |
|
|
Term
| Hepatic Failure - Clinical Signs |
|
Definition
Jaundice_x000D_
Hypoalbuminemia --> peripheral edema_x000D_
Hyerammonemia --> encephalopathy_x000D_
Fetor Hepaticus - distinctive body odor_x000D_
Impaired estrogen metabolism --> hyperestrogenemia --> palmar erythema, spider angiomas, gynecomastia |
|
|
Term
|
Definition
| Clinical triad of chronic liver disease, hypoxemia, and intrapulmonary vascular dilations _x000D_ Associated with refractory ascites |
|
|
Term
| Spontaneous Bacterial Peritonitis |
|
Definition
Infection of ascietes fluid in setting of portal hypertension - SAAG >1.1 _x000D_
Hypoalbuminemia predisposes to infection - decreased complement production_x000D_
Fever, abdominal pain, confusion, renal failure_x000D_
>250 Neutrophils / cc collected via paracentesis is diagnostic_x000D_
Multiple organisms indicates perforated bowel or secondary infection_x000D_
Most common E Coli, Klebsiella, streptococcus_x000D_
Treat with antibiotics and IV albumin to protect kidneys_x000D_ |
|
|
Term
| Portal Hypertension - Varicies |
|
Definition
Portocaval anastamoses - Esophageal varicies at junction of esophagus and stomach_x000D_
Gastric varicies - can also result from focal occlusion of splenic vein in pancreatic cancer_x000D_
Size predicts risk of bleeding - appear as cherry red spots on esophageal mucosa_x000D_
Treat large varicies with non selective beta blockers - reduce portal inflow, reduce pressure_x000D_
IV Octreotide for active bleeds - splanchnic vasoconstrictor_x000D_
Band ligation to prevent or stop bleeding |
|
|
Term
| Portal Hypertension - Hepatic Encephalopathy |
|
Definition
GI bacteria catabolize proteins into ammonia - normally cleared by functional liver_x000D_
Cirrhosis results in elevated blood ammonia levels --> converted to glutamine by astrocytes_x000D_
Results in mental status changes - can progress to deep coma and death_x000D_
Precipitated by hemorrhage (protein meal), tranqulizers, sedatives, azotemia for renal failure_x000D_
Treat with lactulose - non absorbable disaccharide, acidifies GI lumen, traps ammonia |
|
|
Term
| End Stage Liver Disease - Prognosis |
|
Definition
MELD - Model for End Stage Liver Disease_x000D_
Based on creatinine, bilirubin, and INR - score between 6-40_x000D_
Excellent 3 month mortality predictive ability |
|
|
Term
| Cirrhosis - Morphology and Histology |
|
Definition
Bridging fibrous septa link portal tracts together or link portal tract to central veins_x000D_
Parenchymal nodules from cycles of hepatocyte regeneration and scarring_x000D_
Diffuse disruption of architecture of entire liver_x000D_
Collagen type I and III deposited in space of Disse - normally only type IV |
|
|
Term
| Cirrhosis - Pathologic Changes |
|
Definition
Death of hepatocytes, extracellular matrix deposition, and vascular reorganization_x000D_
Surviving hepatocytes proliferate as spherical nodules within fibrous septa_x000D_
Deposition of collagen type I and III in space of Disse - normally only type IV - create fibrotic septal tracts_x000D_
Formation of new vascular channels in fibrotic septa connecting portal vessels to hepatic veins_x000D_
Capillarization of sinusoids - loss of endothelial fenestrations_x000D_
Both processes shunt blood away from liver parenchyma |
|
|
Term
|
Definition
Stellate cell proliferation and activation into myofibroblasts --> deposit type I and III collagen in space of Disse_x000D_
Stellate cells activated by inflammatory processes - TNF, IL 1B, lymphotoxin_x000D_
Myofibroblasts stimulated to contract by endothelin 1 --> constrict sinusoids and increase resistance_x000D_
Surviving hepatocytes proliferate as spherical nodules in confines of fibrous septa |
|
|
Term
| Cirrhosis - Clinical Features |
|
Definition
Asymptomatic until advanced disease progression_x000D_
Anorexia, weight loss, weakness - can progress to signs of hepatic failure_x000D_
Hepatopulmonary syndrome - severely impaired oxygenation_x000D_
Death from progressive liver failure, portal hypertension complication, or hepatocellular carcinoma |
|
|
Term
|
Definition
Blood vessel tumor - occur in many places_x000D_
Most common benign liver tumor_x000D_
Vascular channels in bed of fibrous connective tissue_x000D_
Must diagnose to rule out metastatic tumors |
|
|
Term
|
Definition
Benign hepatocyte neoplasm - normal cell appearance, minimal dysplasia_x000D_
Occur in young women using oral contraceptives - usually regress if OCPs are removed_x000D_
May rupture and cause intraperitoneal hemorrhage, may be mistaken for HCC, rarely transform into HCC_x000D_
Lack portal tracts - solitary arterial and venous vessels distributed throughout tumor |
|
|
Term
|
Definition
Rare malignant tumor of endothelial cells - CD31 + _x000D_
Liver angiosarcoma associated with exposure to vinyl chloride, arsenic, or thorotrast - long latency_x000D_
Highly aggressive, metastasize widely, poor prognosis |
|
|
Term
|
Definition
Most common liver tumor of childhood_x000D_
Derived from fetal / embryonal hepatic cells_x000D_
Activating mutations of Wnt pathway - associated with FAP_x000D_
Epithelial type - cells form acini, tubules, or papillary structures_x000D_
Mixed type - epithelial structures + foci of mesenchymal differentiation - osteoid, cartilage, striated muscle_x000D_
Treat with resection and chemotherapy_x000D_ |
|
|
Term
| Metastatic Liver Tumors - Most Frequent Orign |
|
Definition
GI - 45% - colon most common_x000D_
Lung - 24%_x000D_
Urogenital - 8%_x000D_
Breast - 8%_x000D_
Leukemia, Lymphoma, and Melanoma_x000D_
Primary Liver - 12% |
|
|
Term
| Nodular Regenerative Hyperplasia |
|
Definition
Liver entirely covered with spherical nodules in absence of fibrosis_x000D_
Occurs with reduced oxygenation of liver _x000D_
Diffuse obliteration of portal vein radicles and compensatory increase in arterial blood supply_x000D_
Zone 1 cells receive adequate oxygen supply_x000D_
Zone 3 cells receive sub adequate oxygen supply - become smaller _x000D_
Repetitive alterations of hepatocellular size creates nodular appearance |
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Term
| Focal Nodular Hyperplasia |
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Definition
Well demarcated but poorly encapsulated nodule_x000D_
Focal obliteration of portal vein radicles and compensatory increase in arterial blood supply_x000D_
Central gray stellate scar with fibrous septa radiating out to periphery_x000D_
Central scar contains large arterial vessels_x000D_
Intense lymphocytic infiltrate and bile duct proliferation along septa |
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Term
|
Definition
Infectious agent forms eichonicocal cysts in liver_x000D_
Visualize scolex inside cyst - identify with acid fast stain |
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Term
| Hepatocellular Carcinoma - Major Etiologies |
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Definition
Chronic viral infection - HBV, HCV_x000D_
Chronic alcoholism_x000D_
Non Alcoholic Steatohepatitis_x000D_
Food Contaminants - aflatoxins_x000D_
Tyrosinemia, glycogen storage disease, hemochromatosis, NAFLD, A1AT Deficiency |
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Term
| Hepatocellular Carcinoma - Morphology and Histology |
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Definition
Malignant hepatocyte tumor - can be unifocal, multifocal, or diffusely invasice_x000D_
Well differentiated to anaplastic hepatocyte appearance - no bile ducts in lesion - accumulation of green bile_x000D_
Increased N:C, hyperchromatic nuclei, mitotic figures - serum alpha fetoprotein usually elevated_x000D_
Macrotrabelular architecture - sinusoids at least 4 cells thick instead of normal 1-2_x000D_
Prognosis based on grade of nuclear atypia and presence of vascular invasion |
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Term
| Hepatocellular Carcinoma - Fibrolamellar Carcinoma |
|
Definition
Distinct variant of HCC - not associated with underlying chronic liver disease _x000D_
Malignant hepatocytes, AFP not elevated_x000D_
Central large scar, green appearance from accumulated bile_x000D_
Nests or cords of hepatocytes separated by parallel lamellae of dense collagen bundles_x000D_
Potentially metastatic_x000D_ |
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Term
| Liver - Piecemeal Necrosis |
|
Definition
Death of hepatocytes at limiting plate and erosion of limitng plate_x000D_
Limiting plate = hepatocytes at junction of portal tract and parenchyma_x000D_
Classically was defining feature of active hepatitis - now defined as lymphocyte spilling into parenchyma_x000D_ |
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Term
|
Definition
Classically defined by piecemeal necrosis - death of hepatocytes at limiting plate_x000D_
Now defined by whether lyphocytes are confined to vessels or spill into parenchyma |
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Term
| Liver - Feathery Degeneration |
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Definition
Hepatocyte swelling due to accumulation of bile salts - droplets of bile pigment_x000D_
Commonly seen in cholestatic conditions |
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Term
| Liver - Ballooning Degeneration |
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Definition
Diffuse swelling of hepatocytes - hydropic swelling_x000D_
Cytoplasm appears empty with only scattered eosinophilic remnants of organelles_x000D_
Commonly seen in acute hepatitis |
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Term
| Hepatitis - Activity and Stage |
|
Definition
Activity = degree of inflammation and hepatocyte apoptosis_x000D_
Increased activity is prognostic for faster progression to cirrhosis in HCV infection_x000D_
Stage = degree of fibrosis - no septa, septa, bridging fibrosis, cirrhosis_x000D_
Prognostic indicator for Wilson's and primary biliary cirrhosis |
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Term
| Patterns of Hepatic Fibrosis |
|
Definition
Portal to portal bridging - seen in most chronic conditions - viral, autoimmune_x000D_
Central vein to central vein - seen with etiologies that affect zone 3 - EtOH, Budd Chiari_x000D_
Uniform collagenization of the space of Disse - vitamin A toxicity |
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Term
| Hepatitis C - Molecular Features |
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Definition
Flaviviridae family - ssRNA - single polypeptide with one reading frame processed into functional units_x000D_
5' end encodes conserved nucleocapsids E1 and E2_x000D_
3' end encodes cis acting agents required for viral replication_x000D_
RNA polymerase high error rate --> mutations --> multiple genotypes --> no vaccination ability_x000D_
Most antibodies directed against E2 - E2 is most variable region of genome_x000D_
6 genotypes - 1 most common in US, poor response to therapy - 2,3 respond better_x000D_ |
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Term
| Hepatitis C - Transmission |
|
Definition
Transmitted through blood contact_x000D_
IV drug use, unprotected sex, needle sticks, surgery, children may be infected perinatal |
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Term
| Hepatitis C - Clinical Features |
|
Definition
Majority of patients progress to chronic infection - progress to cirrhosis and HCC_x000D_
May be initially cleared with strong cell mediated immune response - occurs infrequently_x000D_
Evades immune response by inhibiting IFN mediated cellular response_x000D_
Repeated cycles of hepatic damage - episode elevations in serum ALT/AST _x000D_
Risk of HCC increases with repeated injury, regeneration, and cirrhosis |
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Term
| Hepatitis C - Clinical Outcomes |
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Definition
Acute infection --> 30% recover, 70% chronic infection_x000D_
Chronic --> 30% maintain normal ALT, 70% have mild/moderate/severe active infection and damage_x000D_
Chronic active infection --> Cirrhosis --> Decompensation or HCC |
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Term
| Hepatitis C - Treatment Goals and Options |
|
Definition
Goal - sustained responder (cure) - long term undetectable HCV RNA_x000D_
Combination of injectable Pegylated IFN and oral Ribavirn nucleoside analogue _x000D_
Treatment + no decrease in HCV RNA --> non responder, no benefit from further treatment_x000D_
Treatment + decreased HCV RNA --> stop and observe if relapse_x000D_
Viral genotype 1 is less responsive to therapy than 2/3_x000D_
Host IL 28B polymorphism predicts responsiveness to therapy |
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Term
| Hepatitis C - Treatment Side Effects |
|
Definition
IFN - flue like symptoms, depression, insomnia, alopecia, leukopenia, thyroiditis, autoimmunity_x000D_
Ribavirn - Hemolytic anemia, cough, dyspnea, rash, pruritis, insomnia, anorexia - teratogenic |
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Term
| Hepatitis C - Ribavirin Mechanism of Action |
|
Definition
Guanosine analogue_x000D_
Inhibits viral RNA dependent RNA polymerase_x000D_
Induces mutations in HCV RNA, depletes GTP, and modulates T cell response to favor Th1_x000D_
Not effective without IFN treatment_x000D_
Important in preventing relapse after discontinuing treatment |
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Term
| Hepatitis C - IFN Alpha Mechanism of Action |
|
Definition
Delivered as Pegylated form to prolong duration of action and reduce frequency of administration_x000D_
Enhances MHC I expression, amplifies cytotoxic CD 8T and NK cells, enhances macrophage activity_x000D_
Inhibits HCV attachment, uncoating, and activation of cellular RNAses required to process polypeptide viral proteins |
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Term
| Hepatitis C - Directly Acting Antiviral (DAA) Therapy |
|
Definition
Small molecules targeting specific components of viral replication cycle_x000D_
NS 3/4a protease inhibitors_x000D_
NS5B viral polymerase inhibitors_x000D_
NS5A viral assembly inhibitors_x000D_
Improved efficacy, risk of resistance |
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Term
| Hepatitis B - Molecular Features |
|
Definition
Hepadnaviridae family - DNA - partially ds circular genome - four open reading frames_x000D_
HBcAg - nucleocapside core - remains in hepatocyte for viron assembly_x000D_
HBeAg - polypeptide indicates active viral replication_x000D_
HBsAg - surface envelope glycoprotein_x000D_
Pol - polymerase with DNA and RT activity - replication with RNA intermediate - DNA --> RNA --> DNA_x000D_
HBx - transcriptional activator, important in development of HCC |
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Term
| Hepatitis B - Transmission |
|
Definition
Transmitted through blood contact_x000D_
High prevalence - vertical perinatal transmission during childbirth - high carrier rate_x000D_
Intermediate prevalence - horizontal transmission through minor cuts in childhood_x000D_
Low prevalence - unprotected sex, IV drug use |
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Term
|
Definition
HBsAg acute or chronic active infection appears before onset of symptoms_x000D_
HBeAg, HBV DNA, and DNA Pol indicate active viral replication_x000D_
IgM (acute) anti HBc appears before onset of symptoms - replaced by long lasting IgG (chronic)_x000D_
Active Infection - HBsAg, HBeAg, IgM anti HBc_x000D_
Past Infection - IgG anti HBs, anti HBc, and anti HBe_x000D_
Vaccine - IgG anti HBs |
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Term
| Hepatitis B - Clinical Outcomes |
|
Definition
Infection --> acute hepatitis - 70% subclinical, 30% icteric_x000D_
90% recovery from acute, 5% progress to chronic hepatitis, 0.5% experience fulminant hepatitis_x000D_
Chronic hepatitis --> Recovery, Healthy Carrier State, or Cirrhosis (20%)_x000D_
Cirrhosis --> Hepatocellular Carcinoma or Decompensation |
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Term
| Hepatitis B - Phases of Infection |
|
Definition
Immune tolerant - high HBV DNA, low ALT, minimal immune response - seen in neonatal infections_x000D_
Immune clearance - immune response to clear virus, decreasing DNA, increasing ALT_x000D_
Inactive carrier state - no symptoms but can transmit infection, low DNA and ALT_x000D_
Reactivation - Elevated DNA and ALTs |
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Term
| Hepatitis B - Treatment Goals and Indications |
|
Definition
Goal - slow disease progression, reduce liver damage, prevent cirrhosis, decomensation or HCC_x000D_
Goal - HBsAg clearance and seroconversion - difficult to acheive_x000D_
Reduce HBV DNA, loss of HBeAg, develop HBeAg antibodies, Normalize ALT, histologic improvement_x000D_
Indications - chronic patients in immune clearance or reactivation phase_x000D_
HBeAg and HBV DNA elevated for > 6 months, persistent ALT elevation, biopsy evidence of chronic infection_x000D_
Don't treat acute infection or patients in quiescent carrier state |
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Term
| Hepatitis B - Treatment _x000D_ |
|
Definition
Combination injectable Pegylated IFN and oral antiviral nucleoside analogues_x000D_
IFN - Widespread damage, significant side effects, no development of resistance_x000D_
Don't use IFN in patients with cirrhosis --> can cause fulminant liver failure and death_x000D_
Antivirals - lamivudine, adefovir, entecavir - cannot target virus in nuclear phase of cycle_x000D_
Minimal side effects, used in cirrhosis, decompensation, immunocompromised_x000D_
Require longer duration, risk of drug resistant mutants |
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Term
| Hepatitis B - IFN Treatment |
|
Definition
Finite length of therapy, no viral resistance, _x000D_
High relapse rate, significant side effects, cant use in patients with cirrhosis or decompensation_x000D_
Limited use in HBV DNA high / ALT low - immune tolerant phase_x000D_ |
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Term
| Hepatitis B - Nucleoside Analogue Treatment |
|
Definition
Well tolerated, useful in HBeAg negative patients as long term therapy, can use in decompensated cirrhosis_x000D_
High risk of resistant mutations, long term therapy required |
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Term
| Hepatitis A - Molecular Features |
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Definition
| Picornavirus family - ssRNA |
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Term
| Hepatitis A - Transmission |
|
Definition
Spread by ingestion of contaminated water and food_x000D_
Shed in stool for 2-3 weeks before and 1 week after symptoms_x000D_
Fecal - oral transmission in areas with substandard hygiene and sanitations_x000D_
Can be transmitted through shellfish that concentrate HAV from water contaminated with human waste_x000D_
Only transient viremia - blood borne transmission is possible but rare |
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Term
| Hepatitis A - Clinical Features |
|
Definition
Causes acute hepatitis - self limiting, no chronic or carrier states - rarely fulminant_x000D_
Hepatocellular injury mediated by CD8 T cellular immune response_x000D_
Diagnose with serum IgM anti HAV antibodies --> acute active infection_x000D_
IgG antibodies develop for long term immunity |
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Term
|
Definition
Dependent on HBsAG to complete viron assembly_x000D_
Requires preexisting or co infection with HBV |
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Term
| Viral Hepatitis - Chronic Infection |
|
Definition
Symptomatic, biochemical, or serologic evidence of infection > 6 months_x000D_
Young infection --> weaker immune response --> less likely to clear --> more likely to remain chronic_x000D_
Fatigue, malaise, jaundice, spider angiomas, palmar erythema, hepatosplenomegaly_x000D_
Prolonged PT time, hyperglobulinemia, hyperbilirubinemia, elevated Alk Phose_x000D_
Immune complex disease, vasculitis, glomerulonephritis, cryoglobulinemia |
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Term
| Viral Hepatitis - Carrier State |
|
Definition
No manifest symptoms but can transmit organism - reservoir for infecction_x000D_
No HBeAg, low HBV DNA, positive anti HBe antibodies, normal ALT/AST_x000D_
Neonatal / childhood infection --> 90% progress to carrier state_x000D_ |
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Term
| Autoimmune Hepatitis - Pathogenesis |
|
Definition
Chronic and progressive - unknown etiology_x000D_
Cell damage mediated by CD4 ad CD8 T cells producing IFNg and CD8 Cytotoxic T cells_x000D_
Absence of viral serology, elevated serum IgG and gamma globulin, serum autoantibodies_x000D_
Type 1 - anti nuclear, smooth muscle, actin, liver and pancreas antigens_x000D_
Type 2 - anti liver kidney micrsome 1 and anti liver cytosol antibodies |
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Term
| Autoimmune Hepatitis - Clinical Feautres |
|
Definition
May be acute appearance of clinical illness and fulminant onset hepatic encephalopathy_x000D_
May take chronic and progressive course and lead to cirrhosis_x000D_
May show destruction of bile ducts_x000D_
Clusters of plasma cells and lymphocytes in limiting plate observed_x000D_
Treat with immunosuppression |
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Term
| Liver Toxins - Mechanisms of Damage |
|
Definition
Direct toxicity to hepatocytes or biliary epithelial cells --> necrosis and apoptosis_x000D_
Hepatic conversion of xenobiotic to active toxin_x000D_
Toxin acts as a hapten to convert a cellular protein to an immunogenic antigen |
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Term
| Liver Toxins - Acetaminophen |
|
Definition
Dose predictable damage due to p450 conversion into toxic metabolite --> zone 3 hemorrhagic necrosis_x000D_
High doses saturate normal sulfation and glucuronidation clearance mechanisms - consumes NAD_x000D_
Excess is converted by p450 into NAPQ1 --> cytotoxic_x000D_
Chronic EtOH abuse upregulates p450 enzymes and depletes glutothione --> increases susceptibility _x000D_
Treat with mucomyst - competes for p450 binding |
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Term
| Steatosis - Location of Lipid Deposition |
|
Definition
Microvesicular - Reyes, valproic acid, pregnancy_x000D_
Macrovesicular - EtOH, obesity, hyperlipidemia_x000D_
Zone 3 - EtOH, obesity, diabetes_x000D_
Zone 1 - Hep C, AIDS, Kwashiorkor |
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Term
|
Definition
Fatty liver with cellular death due to fat accumulation - inflammation not necessary _x000D_
Ballooning degeneration due to fat accumulation_x000D_
Mallory's Hyaline - ubiquinated intermediate filament cellular inclusions - attracts neutrophils_x000D_
Collagenization of space of Disse (chicken wire), venosclerosis, cirrhosis |
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Term
|
Definition
T cell mediated localized destruction of oral mucosa _x000D_
Initiates on non keratinized mucosa - may extend to keratinized surfaces_x000D_
Increased incidence in patients with ulcerative colitis and other GI disorders |
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|
Term
|
Definition
Oral expression of IBD or GI malignancy - no cutaneous counterpart_x000D_
Yellowish, slightly elevated pustules and ulcerations or oral mucosa_x000D_
Intracellular edema, acantholysis, eosinophilic infiltration _x000D_
May precede onset of intestinal disease_x000D_
Seen in Crohns, Ulcerative Colitis, and as a paraneoplastic phenomenon |
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Term
| Malignant Acanthosis Nigricans |
|
Definition
Paraneoplastic phenomenon _x000D_
Manifestation of GI adenocarcinoma or other internal malignancy_x000D_
May be due to cytokine secretion by tumor cells_x000D_
Finely papillary, hyperkeratotic brownish patches, velvety texture, affects flexural areas of skin |
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